Cavitand compositions and methods of use thereof

ABSTRACT

Cavitand compositions that comprise void spaces are disclosed. The void spaces may be empty, which means that voids are free of guest molecules or atoms, or the void spaces may comprise guest molecules or atoms that are normally in their gas phase at standard temperature and pressure. These cavitands may be useful for industrial applications, such as the separation or storage of gasses. Novel cavitand compounds are also disclosed.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority of U.S. ProvisionalApplication No. 61/614,967, filed Mar. 23, 2012; U.S. ProvisionalApplication No. 61/765,600, filed Feb. 15, 2013; and U.S. ProvisionalApplication No. 61/799,037, filed Mar. 15, 2013.

Any foregoing applications and all documents cited therein or duringtheir prosecution (“application cited documents”) and all documentscited or referenced in the application's cited documents, and alldocuments cited or referenced herein (“herein cited documents”), and alldocuments cited or referenced in herein cited documents, together withany manufacturer's instructions, descriptions, product specifications,and product sheets for any products mentioned herein or in any documentincorporated by reference herein, are hereby incorporated herein byreference, and may be employed in the practice of the invention

Citation or identification of any document in this application is not anadmission that such document is available as prior art to the presentinvention.

BACKGROUND

The industrial importance and broad applicability of microporousmaterials (See Rouquerol, J. et al., Pure & Appl. Chem. 66, 1739-1758(2004)) has long motivated the search for new crystalline materialsexhibiting porosity or inclusion behavior. Inorganic zeolites, activatedcarbons and aluminum phosphates (AlPO₄) play vital roles in commercialapplications (separations, catalysis, ion exchange) but are limited intheir synthetic variability. (See Wilson et al., J. Am. Chem. Soc. 104,1146-1147 (1982)).

For decades, however, it has been recognized that microporous moleculebased materials may be particularly advantageous as the power ofmolecular/organic synthetic chemistry can be brought to bear onmaterials-oriented synthesis. Werner clathrates (see Powell, H. M., J.Chem. Soc. 61-73 (1948); Allison, S. A. & Barrer, R. M., J. Chem. Soc. A1717-1723 (1969)), Dianin's compound (see Dianin, A. P., J. Russ. Phys.Chem. Soc. 36, 1310-1319 (1914); Barrer, R. M.; Shanson, V. H., J. Chem.Soc. Chem. Commun. 1976, 333-334), TPP (see Allcock, H. R., J. Am. Chem.Soc. 86, 2591-2595 (1964); Allcock, H. R., et al., Inorg. Chem. 25,41-47 (1986)) and hydrogen-bonded 3D networks (see Brunet, P., et al.,J. Am. Chem. Soc. 119, 2737-2738 (1997)) to name a few, are notableexamples of discrete molecule microporous materials and have beenintegral in establishing the contemporary field of “crystalengineering”. (See Desiraju, G. R., Angew. Chem. Int. Ed. 46, 8342-8356(2007)).

The confluence of interest in the crystal engineering of molecularmaterials, porous inorganic materials, and metal-ligand self-assemblyculminated in Robson's elucidation of the importance of crystallinecoordination polymers (CPs) (see Robson, R., Dalton Trans. 5113-5131(2008)) and metal-organic frameworks (MOFs) (see MacGillivray, L.Metal-Organic Frameworks: Design and Application, John Wiley & Sons,Hoboken, N.J., (2010); Long, J. R. & Yaghi, O. M. Chem. Soc. Rev. 2009,38, 1201-1507). It also has expanded to the development of covalentorganic frameworks (COFs) (Cote, A. P., et al., Porous, Crystalline,Covalent Organic Frameworks. Science 310, 1166-1170 (2005)) and polymersof intrinsic microporosity (PIMs) (McKeown, N. B. & Budd, P. M. Polymersof Intrinsic Microporosity (PIMs), Encyclopaedia of Polymer Science andTechnology, John Wiley & Sons, Hoboken, N.J., (2002)) among otherscaffolds.

Discrete organic molecular cages (see Tozawa, T., et al., Nat. Mater. 8,973-978 (2009)) that are incapable of close-packing have established theimportance of intrinsically porous molecules (Holst, J. R., et al., Nat.Chem. 2, 915-920 (2010)) that have applicability in selective gasseparations and sorption. Also, materials that exhibit “porosity withoutpores” (Barbour, L. J., Chem. Commun. 1163-1168 (2006)), possessmolecule-sized voids, but no molecular scale channels leading to thesespaces, so permeability is based upon the ability of the small moleculesto diffuse through a barrier; thus by definition, these materials arenot formally porous, e.g., calix[4]arenes.

Calix[n]arenes (Gutsche, D. C., Calixarenes: An Introduction (Monographsin Supramolecular Chemistry (Royal Society of Chemistry, London, 2008))are a class of macrocycles that have, for decades now, receivedattention related to their concave, bowl-like shape, which offers acavity for the complexation of small molecules. So calix[n]arenes andtheir derivatives exhibit a high propensity to form inclusion compoundsin the solid state due to both stabilizing host-guest interactions, andthey have the general inability to form close packed structures in pureform. (Atwood, J. L., Science 296, 2367-2369 (2002)). Numerous studieson p-tert-butylcalix[4]arene helped to elucidate the nature of thesematerials towards gas adsorption as the t-butyl groups provide anobstacle to efficient packing. (Atwood, J. L., Science 298, 1000-1002(2002)). The remarkable gas inclusion properties of these materials hasprompted the study of calix[4]resorcinarenes, and more specifically,cavitand derivatives.

Calix[4]resorcinarenes (Hogberg, A. G. D., J. Am. Chem. Soc. 102,6046-6050 (1980)), synthesized by an acid-catalyzed condensation ofresorcinols and aldehydes, maintain their bowl-like shape throughhydrogen bonding and can be further reacted to yield cavitands viaintramolecular linking of the phenolic groups. (Cram, D. J., Science219, 1177-1183 (1983)). The propensity for cavitands to incorporate aguest unit in their cavity in the solid-state is virtually guaranteed:of the 110 cavitand crystal structures reported in the CambridgeStructural Database (CSD), none contain void space in their packing.

But cavitand crystal structures containing void spaces in crystalpacking could provide useful compositions for industrial applications,such as, separations, catalysis, ion exchange. It is an object of thisinvention to produce cavitand crystal structures with void spaces thatare suitable for industrial use.

SUMMARY OF THE INVENTION

The present invention relates to crystalline compositions of cavitands,cavitand compounds, and methods of using cavitands and cavitandcompositions for certain industrial applications. Crystalline cavitandcompositions of this invention may have characteristics, such ascrystalline packing, that have not been observed in other cavitandcompositions. Additionally, the crystalline cavitand compositions maycomprise void spaces within the crystalline compositions.

Without limitation, a void space maybe a pore or cavity within thecrystalline cavitand composition. The void spaces within the crystallinecomposition may be empty, i.e., free of any molecules or atoms. The voidspaces within the crystalline composition may also comprise gasmolecules or atoms, where a gas is defined as an atom or molecule thatis normally in its gas phase at standard temperature and pressureconditions.

In an embodiment, the present invention relates to compositionscomprising a compound of formula (I):

-   -   and/or stereoisomers thereof; wherein        -   R is H, C₁-C₆ alkyl, halo, or NO₂;        -   R¹ is H, C₁-C₆ alkyl, Ph, (C₁-C₆ alkyl)_(x)Ph,            (C(halo)₃)_(x)Ph, or (halo)_(x)Ph;        -   Y is —CH₂—, C(C₁-C₆ alkyl)₂, or Si(C₁-C₆ alkyl)₂; and        -   x is an integer from 1-3;    -   wherein the composition is in a crystalline form that comprises        void spaces of at least 15 Å³; and    -   wherein the void spaces are free of other atoms and molecules.

In an embodiment of the composition, for the compound of formula (I):

-   -   R is H, CH₃, Br, or NO₂;    -   R¹ is H, CH₃, CH₂CH₃, i-Bu, Ph, 4-CH₃Ph, 4-CF₃Ph, 3,5-(CF₃)₂Ph,        or 3,5-F₂Ph; and    -   Y is —CH₂—, —Si(CH₃)₂—, —Si(CH₃CH₂)₂—, or —Si(i-Pr)₂—.

In another embodiment of the composition, for the compound of formula(I):

-   -   R is H;    -   R¹ is H, CH₃, i-Bu, Ph, 4-CF₃Ph, 3,5-(CF₃)₂Ph, or 3,5-F₂Ph; and    -   Y is —CH₂—, —Si(CH₃)₂—, —Si(CH₃CH₂)₂—, or —Si(i-Pr)₂—;        -   wherein R¹ is not CH₃ when Y is —CH₂—, —Si(CH₃)₂—, or            Si(CH₃CH₂)₂; and        -   wherein R¹ is not Ph when Y is —CH₂—.

In another embodiment of the composition, for the compound of formula(I):

-   -   R is CH₃;    -   R¹ is H, CH₃, CH₂CH₃, i-Bu, 3,5-(CF₃)₂Ph; and    -   Y is —CH₂—, —Si(CH₃)₂—, Si(CH₂CH₃)₂, or —Si(i-Pr)₂—;    -   wherein for R¹ is not H when Y is —CH₂—, —Si(CH₃)₂—; and    -   wherein R¹ is not CH₃ when Y is —CH₂—.

In another embodiment of the composition, for the compound of formula(I):

-   -   R is NO₂;    -   R¹ is H or CH₃; and    -   Y is —CH₂—.

In another embodiment of the composition, for the compound of formula(I):

-   -   R is H, CH₃, or Br;    -   R¹ is H, CH₃, CH₂CH₃, Ph, or 4-CH₃Ph; and    -   Y is —CH₂—, —Si(CH₃)₂—, or Si(CH₂CH₃)₂.

In another embodiment of the composition, the compound of formula (I) isa compound of formula (Ia):

-   -   and/or stereoisomers thereof.

In another embodiment of the composition, the compound of formula (I)has a structure of formula (Ib):

-   -   and/or stereoisomers thereof.

In other embodiments of the composition, the compound of formula (I) isselected from the following (R, R¹, Y):

(H, CH₃, CH₂); (H, i-Bu, CH₂); (H, 4-CF₃Ph, CH₂; (H, 3,5-F₂Ph, CH₂);(CH₃, 3,5-(CF₃)₂Ph, CH₂); (CH₃, CH₃CH₂, CH₂); (CH₃, i-Bu, CH₂); (NO₂, H,CH₂); (H, H, Si(CH₃)₂); (H, i-Bu, Si(CH₃)₂); (CH₃, CH₃, Si(CH₃)₂); (CH₃,CH₃CH₂, Si(CH₃)₂); (CH₃, H, Si(CH₃CH₂)₂); (CH₃, CH₃, Si(CH₃CH₂)₂); (H,H, Si(i-Pr)₂; (H, CH₃, Si(i-Pr)₂); (CH₃, H, Si(i-Pr)₂); and (CH₃, CH₃,Si(i-Pr)₂.

The present invention also relates to cavitand compounds. In a specificembodiment, a cavitand compound has a structure of formula (II).

-   -   and stereoisomers thereof; wherein    -   R³ is H, CH₃, or NO₂;    -   R⁴ is H, CH₃, i-Bu, Ph, 4-CF₃Ph, 3,5-(CF₃)₂Ph or 3,5-F₂Ph;    -   Z is —CH₂—, —Si(CH₃)₂—, —Si(CH₃CH₂)₂—, or —Si(i-Pr)₂—.

An embodiment of formula (II), is a compound of formula (IIa):

-   -   and/or stereoisomers thereof; wherein        -   R⁴ is H, CH₃, i-Bu, Ph, 4-CF₃Ph, 3,5-(CF₃)₂Ph, or 3,5-F₂Ph;            and        -   Z is —CH₂—, —Si(CH₃)₂—, —Si(CH₃CH₂)₂—, or —Si(i-Pr)₂—;            -   wherein R⁴ is not CH₃ when Z is —CH₂—, —Si(CH₃)₂—, or                Si(CH₃CH₂)₂; and        -   wherein R⁴ is not Ph when Z is —CH₂—.

In an embodiment, the compound of formula (IIa) is selected from thefollowing (R⁴, Z):

(CH₃, CH₂); (i-Bu, CH₂; (4-CF₃Ph, CH₂); (3,5-F₂Ph, CH₂; (H, Si(CH₃)₂);(i-Bu, Si(CH₃)₂); (H, Si(i-Pr)₂); (3,5-(CF₃)₂Ph, CH₂); and (CH₃,Si(i-Pr)₂).

An embodiment of formula (II), is a compound of formula (IIb):

-   -   and/or stereoisomers thereof; wherein    -   R⁴ is H, CH₃, CH₂CH₃, i-Bu, or 3,5-(CF₃)₂Ph; and    -   Z is —CH₂—, —Si(CH₃)₂—, Si(CH₂CH₃)₂, or —Si(i-Pr)₂—;        -   wherein R⁴ is not H when Z is —CH₂— or —Si(CH₃)₂—; and        -   wherein R⁴ is not CH₃ when Z is —CH₂—.

In an embodiment, the compound of formula (IIb) is selected from thefollowing (R⁴, Z):

(3,5-(CF₃)₂Ph, CH₂); (CH₃CH₂, CH₂); (i-Bu, CH₂); (CH₃, Si(CH₃)₂);(CH₃CH₂, Si(CH₃)₂); (H, Si(CH₃CH₂)₂); (CH₃, Si(CH₃CH₂)₂); (H,Si(i-Pr)₂); and (CH₃, Si(i-Pr)).

An embodiment of formula (II), is a compound of formula (IIc):

-   -   and/or stereoisomers thereof; wherein        -   R⁴ is H, C₁-C₆ alkyl, Ph, (C₁-C₆ alkyl)_(x)Ph,            (C(halo)₃)_(x)Ph, or (halo)_(x)Ph; and        -   Z is —CH₂—, C(C₁-C₆ alkyl)₂, or Si(C₁-C₆ alkyl)₂;        -   wherein x is an integer from 1-3.

In an embodiment, for the compound formula (IIc) R⁴ is H or CH₃ and Z isCH₂. In another embodiment, R⁴ is H and Z is CH₂.

The present invention also encompasses cavitand compositions comprisingcompounds of formulas (I) and/or (II) that further comprise gas guestmolecules that may be complexed in the void spaces of the cavitand toform host-guest complexes.

The present invention also relates to compositions comprising a compoundof formula (I):

-   -   and/or stereoisomers thereof; wherein:        -   R is H, C₁-C₆ alkyl, halo, or NO₂;        -   R¹ is H, C₁-C₆ alkyl, Ph, (C₁-C₆ alkyl)_(x)Ph,            (C(halo)₃)_(x)Ph, or (halo)_(x)Ph;        -   Y is —CH₂—, C(C₁-C₆ alkyl)₂, or Si(C₁-C₆ alkyl)₂; and        -   x is an integer from 1-3;    -   wherein the composition is a host-guest complex, where at least        some of the void spaces of the composition comprise one or more        guest gas molecules or atoms.

In certain embodiments, the guest gas is selected from one or more ofacetylene, argon, krypton, xenon, carbon dioxide, methane, ethylene,ethane, propyne, propene, propane, fluoromethane, chloromethane,chloroethane, dimethylether, freons, gaseous fluorocarbons,methanethiol, oxygen, nitrogen, and bromomethane.

In certain embodiments, the guest gas is selected from one or more C₁hydrocarbon gasses, C₂ hydrocarbon gasses, and C₃ hydrocarbon gasses.

In certain embodiments, the guest gas is a noble gas. In certainembodiments, the guest gas is argon, krypton, or xenon.

The compounds and compositions of the invention may be characterized bytheir ability to selectively complex gas molecules. This property isuseful for gas separations, wherein two or more gasses may need to beseparated in, for example, an industrial process.

Certain compositions of the invention are capable of forming ahost-guest complex with one or more guest gas molecules within its voidspaces; wherein the guest gas is selected from one or more C₁hydrocarbon gasses, C₂ hydrocarbon gasses, and C₃ hydrocarbon gasses.

In an embodiment, the composition is characterized by forming ahost-guest complex with one or more C₁ hydrocarbon gases selectivelyover one or more C₂ hydrocarbon gasses and/or C₃ hydrocarbon gases. Inanother embodiment, the composition is characterized by forming ahost-guest complex with one or more C₂ hydrocarbon gases selectivelyover one or more C₁ hydrocarbon gasses and/or C₃ hydrocarbon gasses. Inanother embodiment, the composition is characterized by forming ahost-guest complex with one or more C₃ hydrocarbon gases selectivelyover one or more C₁ hydrocarbon gasses and/or C₂ hydrocarbon gasses.

In certain embodiments, the C₁ hydrocarbon gas is methane, the C₂hydrocarbon gas is selected from one or more of ethane, ethylene, andacetylene; and the C₃ hydrocarbon gas is selected from one or more ofpropane, propene, and propyne.

In an embodiment, the composition is capable of forming a host-guestcomplex with one or more guest gas molecules within its void spaces,wherein the one or more guest gas molecule(s) is/are selected from CH₃Cland CH₃CH₂Cl, and wherein the composition is characterized byselectively forming a host-guest complex with CH₃Cl over CH₃CH₂Cl orCH₃CH₂Cl over CH₃Cl.

In another embodiment, the composition is capable of forming ahost-guest complex with guest gas molecules within its void spaces,wherein the one or more guest gas molecule(s) is/are selected from CH₃Cland CH₃OCH₃, and wherein the composition is characterized by selectivelyforming a host-guest complex with CH₃Cl over CH₃OCH₃ or CH₃OCH₃ overCH₃Cl.

In another embodiment, the composition is capable of forming ahost-guest complex with guest gas molecules within its void spaces,wherein the one or more guest gas molecule(s) is/are selected from theAr, Xe, and Kr, and wherein the composition is characterized byselectively forming a host-guest complex with one of Ar, Xe, or Kr overthe others.

In certain embodiments, the cavitand-gas, host-guest complexcompositions may also be used for the confinement of gases at ambienttemperatures that are at least the boiling points of the gases. In anembodiment, the ambient temperature is at least 10° C. greater than theboiling point of the gas. In another embodiment, the ambient temperatureis room temperature or about 20° C. The property of gas confinement hasparticular utility for the separation of gases as well as theconfinement and storage of gasses. In a particular embodiment, theconfined and or separated gasses may be radioactive gasses. In anembodiment, the radioactive gas may be a radioactive isotope of xenon(Xe) and/or krypton (Kr).

The present invention also encompasses methods of using cavitands of theinvention and cavitand compositions of the invention for industrialpurposes, including, but not limited gas separations. In an embodiment,compositions comprising the cavitands of the invention may be used toseparate one or more gasses from other gasses. In another embodiment,compositions comprising the cavitands of the invention may be used toseparate one or more gasses from a solution.

The methods of the present invention are generally useful for theseparation and confinement of gasses. In an embodiment, the presentinvention includes a method for gas separation comprising:

-   -   (i) exposing a sample comprising two or more gasses to a        composition of formula (I); and    -   (ii) selectively forming a host-guest complex between the        composition of formula (I) and one or more of the gasses from        the sample.

In an embodiment, the two or more gasses are selected from acetylene,argon, krypton, xenon, carbon dioxide, methane, ethylene, ethane,propyne, propene, propane, fluoromethane, chloromethane, chloroethane,dimethylether, freons, gaseous fluorocarbons, methanethiol, oxygen,nitrogen, and bromomethane.

In an embodiment, the present invention relates to methods for theseparation of hydrocarbon gasses. As a non-limiting illustration,hydrocarbon gasses may be separated on the basis of length, i.e., numberof carbon atoms, structure, i.e., straight chained versus branched, orsaturation, i.e., the separation of alkanes, alkenes, and/or alkynes. Inan embodiment, compositions of the invention are capable of doingseparations of hydrocarbons including, but not limited to, C₁hydrocarbons, C₂ hydrocarbons, and C₃ hydrocarbons.

In an embodiment, the method comprises separating propane and propene.In another embodiment, the method comprises separating ethylene andethane.

In another embodiment, the invention relates to the separation of gasescontaining functional groups. For example, the compositions of theinvention may be used to separate haloalkanes or ethers that arenormally in their gas phase at standard temperature and pressure. In anembodiment, the compositions are capable of separating dimethyl etherfrom chloromethane and/or chloroethane. In another embodiment, thecompositions are capable of separating chloromethane and chloroethane.

The present invention also relates to a method of gas storagecomprising:

-   -   (i) exposing a sample comprising one or more gasses to an empty        crystalline cavitand composition of the invention, and    -   (ii) forming a host-guest complex between the composition and        one or more gasses from (i) the gas;        -   wherein the complex is capable of retaining at least 95% of            the gas at an ambient temperature that is at least 10° C.            greater than the boiling point of the gas.

In an embodiment, the ambient temperature is at least 10° C. greaterthan the boiling point of the gas. In another embodiment, the ambienttemperature is room temperature or 20° C. The property of gasconfinement has particular utility for the separation of gases as wellas the storage of gasses, for example for toxic or dangerous gasses. Ina particular embodiment, the confined and or separated gasses may beradioactive gasses. In an embodiment, the radioactive gas may be aradioactive isotope of xenon (Xe) and/or krypton (Kr).

In an embodiment, the present invention also relates to a process formaking crystalline cavitand compositions, wherein the compositionscomprise voids that are free of solvent molecules. In anotherembodiment, the present invention relates to a process for makingcrystalline cavitand compositions, wherein the compositions comprisevoids that are free of any guest molecules, i.e., empty cavitandcrystals. In another embodiment, the present invention relates to aprocess for making crystalline cavitand compositions, wherein thecompositions comprise voids containing guest molecules or atoms withinthe voids, wherein the guest molecules are molecules or atoms that arein gas phase at standard temperature and pressure.

In an embodiment, a process for making empty cavitand compositions ofthe invention comprises:

-   -   (i) forming a crystalline cavitand composition;    -   (ii) heating the crystals in order to eliminate any molecules        that are in the void spaces of the crystalline cavitand        compositions; and    -   (iii) verifying that the void spaces of the composition are free        of other molecules and atoms by analytical techniques known in        the art.

In an embodiment, the analytical technique for verifying that voidspaces are free of molecules is known in the art. In particularembodiments, the analytical technique is x-ray crystallography orthermogravimetric analysis (TGA).

It is further noted that the invention does not intend to encompasswithin the scope of the invention any previously disclosed product orcomposition, process of making the product or composition, or method ofusing the product or composition, which meets the written descriptionand enablement requirements of the USPTO (35 U.S.C. 112, firstparagraph) or the EPO (Article 83 of the EPC), such that applicant(s)reserve the right and hereby disclose a disclaimer of any previouslydescribed product, method of making the product or process of using theproduct.

These and other embodiments are disclosed or are apparent from andencompassed by the following Detailed Description.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1: Thermal ellipsoid plots of (left to right) empty formula (Ia)(@100 K), formula (Ia) (at 298 K), CH₂Cl₂@formula (Ia), BrCH₂Cl@formula(Ia), and CH₂Br₂@formula (Ia) at 50% probability level.

FIG. 2: Powder X-ray Diffraction (PXRD) patterns of a) empty formula(Ia)—simulated (298 K), b) empty formula (Ia) (298 K), c) formula (Ia)from propane experiment (298 K) d) CH₂Cl₂@formula (Ia) (298 K), e)CH₂Cl₂@formula (Ia)—simulated (100 K), f) CH₃Cl@formula (Ia) (298 K), g)EtCl@formula (Ia) (298 K), h) x(CH₃OCH₃)@formula (Ia) (298 K), i)CH₃CHCH₂@formula (Ia) (298 K), j) NO₂CH₃@formula (Ia)—simulated (100 K),k) BrCH₂Cl@formula (Ia)—simulated (100 K), 1) CH₂Br₂@formula(Ia)—simulated (100 K), m) (CH₂Cl)₂@formula (Ia)—simulated (100 K), n)CHCl₃@formula (Ia)—simulated (100 K).

FIG. 3: Thermogravimetric analysis of various x(guest)@formula (Ia)inclusion compounds with corresponding % weight loss and T_(max) values.

FIG. 4: Isostructural crystal packing of a) empty formula (Ib),illustrating the unoccupied 28 Å³ ultramicrocavities, b)0.85CH₂Cl₂@formula (Ib), and c) the partial hydrate xH₂O@formula (Ib)(x<0.4), as seen for one layer of molecules packed in the bc plane. d)Spacefill model of the empty and CH₂Cl₂-occupied formula (Ib) cavitandsas viewed from the top of the bowls. Cavity volumes in a) and b) aredepicted (1.4 Å probe) and guests are shown as spacefill models.

FIG. 5: TGA of empty formula (Ib) (black) and derivative weight curve.Inset: magnified view.

FIG. 6: Single crystal structures of several isostructuralx(gas/solvent)@formula (Ib) (x≤1) clathrates, along with summarystructural parameters V_(cell), Δτ, ϕ, and d, defined in the text. TheCH₃CCH@formula (Ib) complex is taken from the structure ofCH₃CCH@formula (Ib).2CHCl₃.

FIG. 7: a) TGA of selected x(gas)@formula (Ib) (x≤1) clathrateshighlighting the unusual kinetic stability of the clathrates. Themaximum of the semitransparent derivative mass loss curves is defined asT_(max) and T_(max)−T_(bp) (=315° C., Ar; 292° C., Kr; 279° C., Xe; 187°C., CO₂) may be considered a semi-quantitative measure of the relativeextent of guest confinement. a) Room temperature, P_(H2O)=0.028(3) barwater vapor uptake kinetics as measured by SCXRD analysis of anoriginally empty crystal of formula (Ib). The equilibrium occupancy is0.32H₂O@formula (Ib).

FIG. 8: Selectivity profile for MeCl vs. EtCl with formula (Ib) as ahost. Diagonal line denotes no selectivity (K=1); curved lines showselectivity 2 esds above and below the determined K_(MeCl:EtCl). Axesare labelled as mole fractions of both gases in the starting solution(X) and the host after the experiment (Y). Individual shapes highlightwhat method of competition experiments were performed for specific datapoint (diamond—cooling, circle—evaporation, square—precipitation,x—solid-solution).

FIG. 9: Selectivity profile for MeCl vs. DME with formula (Ib) as ahost. Diagonal line denotes no selectivity (K=1); curved lines showselectivity 2 esds above and below the determined K_(MeCl:DME). Axes arelabelled as mole fractions of both gases in the starting solution (X)and the host after the experiment (Y). Individual shapes highlight whatmethod of competition experiments were performed for specific data point(diamond—cooling, circle—evaporation, square—precipitation,x—solid-solution).

FIG. 10: Swelling of the formula (Ib) cavity largely entails an outwardswinging of the O—Si—O linkages such that the angles between the planesdefined by the O—Si—O linkages and the plane defined by the upper rimatoms of the pseudo 4-fold symmetric cavitand (angle τ) are all moreacute.

FIG. 11: Thermal ellipsoid plots of solid-solutions from competitioncrystal growth experiments shown with 50% probability ellipsoids.

FIG. 12: Stereochemistry of cavitands of formula (I). The figure alsodepicts two stereoisomers, rccc and rctt, of formula (I) where R is H,R¹ is Ph, and Y is CH₂.

FIG. 13: Demonstration of the substituent modification effects forcompositions comprising compounds of formula (I). Varying the R, R¹, Ygroups affect the volume of the void space and crystal packing.

FIG. 14: Uptake of water vapor by a Me, H, SiMe₂ cavitand crystalcomposition.

FIG. 15: TGA of 0.77CH₃@formula (Ib).

FIG. 16: Thermogravimetric analysis-mass spectrometry (TGA-MA) of0.81Xe@formula (Ib).

FIG. 17: Thermogravimetric analysis-mass spectrometry (TGA-MA) of0.54Kr@formula (Ib) after 7 days at 298K.

FIG. 18: Stereoisomeric effects on the void spaces of rccc-H,Ph,CH₂ andrctt-Me,Ph,CH₂.

FIG. 19: Examples of guest-free cavitands: (Me,i-Bu,CH₂),(H,4-MePh,CH₂), (H,3-CF₃,CH₂), (H,Ph,CH₂), (NO₂,H,CH₂), (Br,CH₃,CH₂),(rctt-Me,4-CF₃,CH₂)

DETAILED DESCRIPTION

The cavitand compositions described herein, provide for crystallinestructures that contain void spaces. These void spaces are capable ofthe selective uptake of certain chemical compounds, but not others. Thecavitand compositions of the present invention open up cavitandchemistry for new industrial applications, such as gas separations,where there is demand for new efficient methods.

In an embodiment, the present invention relates to compositionscomprising a compound of formula (I):

-   -   and/or stereoisomers thereof; wherein        -   R is H, C₁-C₆ alkyl, halo, or NO₂;        -   R¹ is H, C₁-C₆ alkyl, Ph, (C₁-C₆ alkyl)_(x)Ph,            (C(halo)₃)_(x)Ph, or (halo)_(x)Ph;        -   Y is —CH₂—, C(C₁-C₆ alkyl)₂, or Si(C₁-C₆ alkyl)₂; and        -   x is an integer from 1-3;    -   wherein the composition is in a crystalline form that comprises        void spaces of at least 15 Å³; and    -   wherein the void spaces are free of other atoms and molecules.

Cavitands of formula (I), as described herein, may also be referred toby the R, R¹, and Y groups as R,R¹,Y. For example, a cavitand of formula(I), wherein R is H, R¹ is CH₃, and Y is CH₂ could alternately bereferred to as H,Me,CH₂, or similar equivalents.

The void spaces of the crystalline compositions can vary in size. In anembodiment, the void space is greater than 15 Å³. In an embodiment, thevoid space is greater than 20 Å³. In an embodiment, the void space isgreater than 25 Å³.

In another embodiment, the void space is greater than 50 Å³. In certainembodiments the void space can range from about 15 Å³ to about 500 Å³,15 Å³ to about 400 Å³, 15 Å³ to about 300 Å³, 15 Å³ to about 200 Å³, 15Å³ to about 100 Å³, 15 Å³ to about 50 Å³, or 15 Å³ to about 25 Å³.

In other embodiments, the void space can range from about 20 Å³ to about500 Å³, 20 Å³ to about 400 Å³, 20 Å³ to about 300 Å³, 20 Å³ to about 200Å³, 20 Å³ to about 100 Å³, 20 Å³ to about 50 Å³, or 20 Å³ to about 25Å³.

In other embodiments, the void space can range from about 25 Å³ to about500 Å³, 25 Å³ to about 400 Å³, 25 Å³ to about 300 Å³, 25 Å³ to about 200Å³, 25 Å³ to about 100 Å³, or 25 Å³ to about 50 Å³.

In other embodiments, the void space can range from about 50 Å³ to about500 Å³, 50 Å³ to about 400 Å³, 50 Å³ to about 300 Å³, 50 Å³ to about 200Å³, or 50 Å³ to about 100 Å³.

In order to determine whether the void spaces of compositions of theinvention are free of other atoms or molecules, analytical techniquessuch as thermogravimetric analysis (TGA) or x-ray crystallography may beused. For TGA, the composition is considered empty if there is no massloss upon heating up to the sublimation temperature of the composition.

No mass loss in the context of TGA for compositions of the presentinvention is intended to include no more than about 20%, 15%, 10%, 5%,3%, 2%, 1%, 0.5%, 0.2%, 0.1%, or no detectable mass loss.

In certain embodiments of the present invention, the TGA of cavitandcompositions yields a weight loss of from about 0% to about 20%; about0% to about 15%, about 0% to about 10%, about 0% to about 5%, about 0%to about 2%, about 0% to about 1%, about 0% to about 0.5%, about 0% toabout 0.2%, or about 0% to about 0.1% of the composition up to thecompositions sublimation temperature.

In an embodiment, the present invention relates to compositionscomprising a compound of formula (I), as described above, but where atleast some of the void spaces of the composition comprise one or moreguest gas molecules. The guest molecules contained within the voidspaces are typically in a gas phase at standard temperature andpressure. The resultant complexes may be described as, for example,host-guest complexes, cavitand-guest complexes, or cavitand-gascomplexes. In certain embodiments, the ratio of gas to cavitand is fromabout 0.1 to 2.0, 0.1 to 1.0, 0.1 to 0.8, 0.1 to 0.5, 0.1 to 0.3, 0.3 to2.0, 0.3 to 1.0, 0.3 to 0.8, 0.3 to 0.5, 0.5 to 2.0, 0.5 to 1.0, 0.5 to0.8, 0.8 to 2.0, 0.8 to 1.0, or 1.0 to 2.0.

In certain embodiments, the guest gas is selected from one or more ofacetylene, argon, krypton, xenon, carbon dioxide, methane, ethylene,ethane, propyne, propene, propane, fluoromethane, chloromethane,chloroethane, dimethylether, freons, gaseous fluorocarbons,methanethiol, oxygen, nitrogen, and bromomethane.

In certain embodiments, the gas phase molecule in the void space maycomprise one or more of the following gasses: methane, ethane, ethene,ethyne, acetylene, propane, propene, propyne, butane, 1- or 2-butene, 1-or 2-butyne, bromomethane, chloromethane, chloroethane, fluoromethane,dimethyl ether, methane thiol, carbon dioxide, hydrogen, helium, argon,krypton, neon, xenon, nitrogen, oxygen, and other gas moleculesgenerally contained in atmospheric air.

In certain embodiments, compounds of formula (I) can be more than onestereoisomer. For example, when R¹ is not a hydrogen atom (—H—), thecarbon atom to which R¹ is bound is chiral. Chemical formula of thepresent invention can be generally assumed to include all possiblestereoisomers, unless otherwise stated. In certain embodiments,compounds of the invention are the rccc or rctt stereoisomer. In certainembodiments, the chemical compounds of the invention may bestereoisomerically pure. Stereoisomeric purity may be defined as atleast 90%, 95%, 97%, 99%, or 99.5% stereoisomeric purity as determinedby analytical methods well known to those of ordinary skill in the art.

In an embodiment, when the compound of formula (I) can be one or morestereoisomer, the compositions of the present invention may comprise acompound of formula (I) that is a single stereoisomer. In anotherembodiment of the composition, the compound of formula (I) may bepresent as a mixture of stereoisomers.

Convention regarding stereoisomerism of cavitands is illustrated in FIG.12. In some embodiments, the compound of a compound of formula (I) isthe rccc stereoisomer. In some embodiments, the stereochemistry of acompound of formula (I) is the rctt stereoisomer.

In an embodiment, the crystalline cavitand compositions of the presentinvention comprise void spaces that are empty. The empty void spaces maybe accessible to certain molecules, but inaccessible to other molecules.This property allows the cavitand compositions of the present inventionto selectivity take up guest molecules or atoms, for example, gasmolecules or atoms. The guest molecules or atoms may be complexed and/orencapsulated within the void spaces of the composition. In anembodiment, the guest(s) is/are chemicals that are in a gas phase atstandard temperature and pressure.

In another embodiment, the present invention relates to compositionscomprising one or more cavitand compounds selected from formulas (I),(Ia), (Ib), (II), (IIa), (IIb), and (IIc).

Though the compositions of the present invention may not formally beporous, the void spaces or cavities within the compositions maynonetheless be accessible to small molecules and gases under conditionsdifferent from the low-temperature gas sorption experimentstraditionally used to characterize porous material. This suggests thatnanocrystal or mechanochemical approaches may offer opportunities toaddress potentially slow approach-to-equilibrium kinetics in thesematerials. Moreover, the systematic study of ultramicrocavity andnanospace structure, particularly in response to the presence ofsuitable atomic or small molecule probe species, offers opportunities toexperimentally examine issues of structural flexibility andaccommodation at the sub-angstrom length scale, features that cannotoften be studied in large-pore materials.

It is revealed that crystalline compounds of formula (I) are highlycapable of highly selective gas capture during crystallization (e.g.,ethane vs. propane, chloromethane vs. dimethyl ether, ethylene vs.ethane, propene vs. propane, chloromethane vs. chloroethane, etc.) andconfines highly volatile gases at unusually high temperatures. Moreover,while crystals are permeable to certain small molecules without anydisruption of their single crystallinity, the kinetics of gas egress arequalitatively slow in comparison to open-pore materials, but areintriguingly highly guest dependent.

For gas uptake to form host-guest complexes of the present invention,may be achieved when the gas molecule or atom is in the gas phase.Alternatively, for gas uptake in certain embodiments, the gas moleculeor atom may be in its liquid phase.

For gas storage, the host-guest complexes of the present invention arecapable of retaining gases at ambient temperatures that are greater thenthe boiling point of the gas, but no more than the sublimationtemperature of the composition. In certain embodiments, the host-guestcomplexes are capable of retaining gasses at an ambient temperature thatis at least 5° C., 10° C., 20° C., 30° C., 40° C., 50° C., 75° C., 100°C., 150° C., 200° C., 250° C., or 300° C. greater than boiling point ofthe guest atom or molecule.

In certain embodiments, a guest may be retained within the host-guestcomplex at an ambient temperature of at least −150° C., −100° C., −50°C., −25° C., 0° C., 10° C., 20° C., 30° C., 40° C., 50° C., 75° C., 100°C., 150° C., or 200° C. In certain embodiments, the ambient temperatureis from about −150° C. to −100° C., −100° C. to −50° C., −50° C. to −25°C., −25° C. to 0° C., 0° C. to 10° C., 0° C. to 20° C., 0° C. to 50° C.,20° C. to 50° C., 20° C. to 100° C., or 50° C. to 200° C.

In the host-guest complex, at the elevated temperatures described above,the guest gas is at least 50% retained, 75% retained, 80% retained, 85%retained, 90% retained, 95% reatine, 97% retained, 98% retained, 99%retained, 99.5% retained, or fully retained within instrumentmeasurement limits.

For the first time, guest-free single crystal structures of numerousresorcinarene-derived cavitands have been synthesized. And it has beenfound that, as expected, in cases where it is sterically infeasible forperipheral functional groups to fully penetrate the bowl-like molecularcavity, empty molecule-sized ultramicrocavities (i.e. spheroidal pores),intrinsic to the molecule, are present in the structures.

DEFINITIONS

All definitions, as defined and used herein, should be understood tocontrol over dictionary definitions, definitions in documentsincorporated by reference, and/or ordinary meanings of the definedterms.

For purposes of this invention, the chemical elements are identified inaccordance with the Periodic Table of the Elements, CAS version,Handbook of Chemistry and Physics, 67th Ed., 1986-87, inside cover.

The articles “a” and “an” are used herein to refer to one or to morethan one (i.e., to at least one) of the grammatical object of thearticle. By way of example, “an element” means one element or more thanone element.

The phrase “and/or,” as used herein in the specification and in theclaims, should be understood to mean “either or both” of the elements soconjoined, i.e., elements that are conjunctively present in some casesand disjunctively present in other cases. Multiple elements listed with“and/or” should be construed in the same fashion, i.e., “one or more” ofthe elements so conjoined. Other elements may optionally be presentother than the elements specifically identified by the “and/or” clause,whether related or unrelated to those elements specifically identified.Thus, as a non-limiting example, a reference to “A and/or B”, when usedin conjunction with open-ended language such as “comprising” can refer,in one embodiment, to A only (optionally including elements other thanB); in another embodiment, to B only (optionally including elementsother than A); in yet another embodiment, to both A and B (optionallyincluding other elements); etc.

As used herein in the specification and in the claims, “or” should beunderstood to have the same meaning as “and/or” as defined above. Forexample, when separating items in a list, “or” or “and/or” shall beinterpreted as being inclusive, i.e., the inclusion of at least one, butalso including more than one, of a number or list of elements, and,optionally, additional unlisted items. Only terms clearly indicated tothe contrary, such as “only one of” or “exactly one of,” or, when usedin the claims, “consisting of,” will refer to the inclusion of exactlyone element of a number or list of elements. In general, the term “or”as used herein shall only be interpreted as indicating exclusivealternatives (i.e., “one or the other but not both”) when preceded byterms of exclusivity, such as “either,” “one of,” “only one of,” or“exactly one of” “Consisting essentially of,” when used in the claims,shall have its ordinary meaning as used in the field of patent law.

As used herein in the specification and in the claims, the phrase “atleast one,” in reference to a list of one or more elements, should beunderstood to mean at least one element selected from any one or more ofthe elements in the list of elements, but not necessarily including atleast one of each and every element specifically listed within the listof elements and not excluding any combinations of elements in the listof elements. This definition also allows that elements may optionally bepresent other than the elements specifically identified within the listof elements to which the phrase “at least one” refers, whether relatedor unrelated to those elements specifically identified. Thus, as anon-limiting example, “at least one of A and B” (or, equivalently, “atleast one of A or B,” or, equivalently “at least one of A and/or B”) canrefer, in one embodiment, to at least one, optionally including morethan one, A, with no B present (and optionally including elements otherthan B); in another embodiment, to at least one, optionally includingmore than one, B, with no A present (and optionally including elementsother than A); in yet another embodiment, to at least one, optionallyincluding more than one, A, and at least one, optionally including morethan one, B (and optionally including other elements); etc.

It should also be understood that, unless clearly indicated to thecontrary, in any methods claimed herein that include more than one stepor act, the order of the steps or acts of the method is not necessarilylimited to the order in which the steps or acts of the method arerecited.

In the claims, as well as in the specification above, all transitionalphrases such as “comprising,” “including,” “carrying,” “having,”“containing,” “involving,” “holding,” “composed of,” and the like are tobe understood to be open-ended, i.e., to mean including but not limitedto. Only the transitional phrases “consisting of” and “consistingessentially of” shall be closed or semi-closed transitional phrases,respectively, as set forth in the United States Patent Office Manual ofPatent Examining Procedures, Section 2111.03.

The term “about,” as used herein in reference to quantitativemeasurements, refers to the indicated value plus or minus 10%.

The term “heteroatom” as used herein is art-recognized and refers to anatom of any element other than carbon or hydrogen. Illustrativeheteroatoms include boron, nitrogen, oxygen, phosphorus, sulfur andselenium.

The term “alkenyl” as used herein means a straight or branched chainhydrocarbon containing from 2 to 10 carbons and containing at least onecarbon-carbon double bond formed by the removal of two hydrogens.Representative examples of alkenyl include, but are not limited to,ethenyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl,5-hexenyl, 2-heptenyl, 2-methyl-1-heptenyl, and 3-decenyl.

The term “alkoxy” as used herein means an alkyl group, as definedherein, appended to the parent molecular moiety through an oxygen atom.Representative examples of alkoxy include, but are not limited to,methoxy, ethoxy, propoxy, 2-propoxy, butoxy, tert-butoxy, pentyloxy, andhexyloxy.

The term “arylalkoxy” and “heteroalkoxy” as used herein means an arylgroup or heteroaryl group, as defined herein, appended to the parentmolecular moiety through an alkoxy group, as defined herein.Representative examples of arylalkoxy include, but are not limited to,2-chlorophenylmethoxy, 3-trifluoromethylethoxy, and 2,3-methylmethoxy.

The term “arylalkyl” as used herein means an aryl group, as definedherein, appended to the parent molecular moiety through an alkyl group,as defined herein. Representative examples of alkoxyalkyl include, butare not limited to, tert-butoxymethyl, 2-ethoxyethyl, 2-methoxyethyl,and methoxymethyl.

The term “alkyl” means a straight or branched chain hydrocarboncontaining from 1 to 10 carbon atoms. Representative examples of alkylinclude, but are not limited to, methyl, ethyl, n-propyl, iso-propyl,n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, isopentyl,neopentyl, and n-hexyl.

The term “alkylene,” is art-recognized, and as used herein pertains to abidentate moiety obtained by removing two hydrogen atoms of an alkylgroup, as defined above.

The term “alkylcarbonyl” as used herein means an alkyl group, as definedherein, appended to the parent molecular moiety through a carbonylgroup, as defined herein. Representative examples of alkylcarbonylinclude, but are not limited to, acetyl, 1-oxopropyl,2,2-dimethyl-1-oxopropyl, 1-oxobutyl, and 1-oxopentyl.

The term “alkylthio” as used herein means an alkyl group, as definedherein, appended to the parent molecular moiety through a sulfur atom.Representative examples of alkylthio include, but are not limited,methylthio, ethylthio, tert-butylthio, and hexylthio. The terms“arylthio,” “alkenylthio” and “arylakylthio,” for example, are likewisedefined.

The term “alkynyl” as used herein means a straight or branched chainhydrocarbon group containing from 2 to 10 carbon atoms and containing atleast one carbon-carbon triple bond. Representative examples of alkynylinclude, but are not limited, to acetylenyl, 1-propynyl, 2-propynyl,3-butynyl, 2-pentynyl, and 1-butynyl.

The term “amino” as used herein refers to radicals of both unsubstitutedand substituted amines appended to the parent molecular moiety through anitrogen atom. The additional groups appended to the nitrogen areindependently hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl,arylcarbonyl, or formyl. Representative examples include, but are notlimited to methylamino, acetylamino, and acetylmethylamino.

The term “aromatic” refers to a planar or polycyclic structurecharacterized by a cyclically conjugated molecular moiety containing4n+2 electrons, wherein n is the absolute value of an integer. Aromaticmolecules containing fused, or joined, rings also are referred to asbicylic aromatic rings. For example, bicyclic aromatic rings containingheteroatoms in a hydrocarbon ring structure are referred to as bicyclicheteroaryl rings.

The term “aryl,” as used herein means a phenyl group or a naphthylgroup. The aryl groups of the present invention can be optionallysubstituted with 1, 2, 3, 4 or 5 substituents independently selectedfrom the group consisting of alkenyl, alkoxy, alkoxycarbonyl,alkoxysulfonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkylsulfonyl,alkylthio, alkynyl, amido, amino, carboxy, cyano, formyl, halo,haloalkoxy, haloalkyl, hydroxyl, hydroxyalkyl, mercapto, nitro,phosphinyl, silyl and silyloxy.

The term “arylene,” is art-recognized, and as used herein pertains to abidentate moiety obtained by removing two hydrogen atoms of an arylring, as defined above.

The term “arylalkyl” or “aralkyl” as used herein means an aryl group, asdefined herein, appended to the parent molecular moiety through an alkylgroup, as defined herein. Representative examples of arylalkyl include,but are not limited to, benzyl, 2-phenylethyl, 3-phenylpropyl, and2-naphth-2-ylethyl.

The term “aryloxy” as used herein means an aryl group, as definedherein, appended to the parent molecular moiety through an oxygen. Theterm “heteroaryloxy” as used herein means a heteroaryl group, as definedherein, appended to the parent molecular moiety through an oxygen.

The term “carbonyl” as used herein means a —C(O)— group.

The term “carboxy” as used herein means a —CO₂H group.

The term “cycloalkyl” as used herein means monocyclic or multicyclic(e.g., bicyclic, tricyclic, etc.) hydrocarbons containing from 3 to 12carbon atoms that is completely saturated or has one or more unsaturatedbonds but does not amount to an aromatic group. Examples of a cycloalkylgroup include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl,cyclohexyl and cyclohexenyl.

The term “cycloalkoxy” as used herein means a cycloalkyl group, asdefined herein, appended to the parent molecular moiety through anoxygen.

The term “cyano” as used herein means a —CN group.

The term “halo” or “halogen” means —Cl, —Br, —I or —F.

The term “haloalkyl” means at least one halogen, as defined herein,appended to the parent molecular moiety through an alkyl group, asdefined herein. Representative examples of haloalkyl include, but arenot limited to, chloromethyl, 2-fluoroethyl, trifluoromethyl,pentafluoroethyl, and 2-chloro-3-fluoropentyl.

The term “heterocyclyl”, as used herein include non-aromatic, ringsystems, including, but not limited to, monocyclic, bicyclic andtricyclic rings, which can be completely saturated or which can containone or more units of unsaturation, for the avoidance of doubt, thedegree of unsaturation does not result in an aromatic ring system) andhave 3 to 12 atoms including at least one heteroatom, such as nitrogen,oxygen, or sulfur. For purposes of exemplification, which should not beconstrued as limiting the scope of this invention, the following areexamples of heterocyclic rings: azepines, azetidinyl, morpholinyl,oxopiperidinyl, oxopyrrolidinyl, piperazinyl, piperidinyl, pyrrolidinyl,quinicludinyl, thiomorpholinyl, tetrahydropyranyl and tetrahydrofuranyl.The heterocyclyl groups of the invention are substituted with 0, 1, 2,3, 4 or 5 substituents independently selected from alkenyl, alkoxy,alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy,alkylsulfonyl, alkylthio, alkynyl, amido, amino, carboxy, cyano, formyl,halo, haloalkoxy, haloalkyl, hydroxyl, hydroxyalkyl, mercapto, nitro,phosphinyl, silyl and silyloxy.

The term “heteroaryl” as used herein include aromatic ring systems,including, but not limited to, monocyclic, bicyclic and tricyclic rings,and have 3 to 12 atoms including at least one heteroatom, such asnitrogen, oxygen, or sulfur. For purposes of exemplification, whichshould not be construed as limiting the scope of this invention:azaindolyl, benzo[b]thienyl, benzimidazolyl, benzofuranyl, benzoxazolyl,benzothiazolyl, benzothiadiazolyl, benzotriazolyl, benzoxadiazolyl,furanyl, imidazolyl, imidazopyridinyl, indolyl, indolinyl, indazolyl,isoindolinyl, isoxazolyl, isothiazolyl, isoquinolinyl, oxadiazolyl,oxazolyl, purinyl, pyranyl, pyrazinyl, pyrazolyl, pyridinyl,pyrimidinyl, pyrrolyl, pyrrolo[2,3-d]pyrimidinyl,pyrazolo[3,4-d]pyrimidinyl, quinolinyl, quinazolinyl, triazolyl,thiazolyl, thiophenyl, tetrahydroindolyl, tetrazolyl, thiadiazolyl,thienyl, thiomorpholinyl, triazolyl or tropanyl. The heteroaryl groupsof the invention are substituted with 0, 1, 2, 3, 4 or 5 substituentsindependently selected from alkenyl, alkoxy, alkoxycarbonyl,alkoxysulfonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkylsulfonyl,alkylthio, alkynyl, amido, amino, carboxy, cyano, formyl, halo,haloalkoxy, haloalkyl, hydroxyl, hydroxyalkyl, mercapto, nitro,phosphinyl, silyl and silyloxy.

The term “heteroarylene,” is art-recognized, and as used herein pertainsto a bidentate moiety obtained by removing two hydrogen atoms of aheteroaryl ring, as defined above.

The term “heteroarylalkyl” or “heteroaralkyl” as used herein means aheteroaryl, as defined herein, appended to the parent molecular moietythrough an alkyl group, as defined herein. Representative examples ofheteroarylalkyl include, but are not limited to, pyridin-3-ylmethyl and2-(thien-2-yl)ethyl.

The term “hydroxy” as used herein means an —OH group.

The term “hydroxyalkyl” as used herein means at least one hydroxy group,as defined herein, is appended to the parent molecular moiety through analkyl group, as defined herein. Representative examples of hydroxyalkylinclude, but are not limited to, hydroxymethyl, 2-hydroxyethyl,3-hydroxypropyl, 2,3-dihydroxypentyl, and 2-ethyl-4-hydroxyheptyl.

The term “mercapto” as used herein means a —SH group.

The term “nitro” as used herein means a —NO₂ group.

The term “silyl” as used herein includes hydrocarbyl derivatives of thesilyl (H₃Si—) group (i.e., (hydrocarbyl)₃Si—), wherein a hydrocarbylgroups are univalent groups formed by removing a hydrogen atom from ahydrocarbon, e.g., ethyl, phenyl. The hydrocarbyl groups can becombinations of differing groups which can be varied in order to providea number of silyl groups, such as trimethylsilyl (TMS),tert-butyldiphenylsilyl (TBDPS), tert-butyldimethylsilyl (TBS/TBDMS),triisopropylsilyl (TIPS), and [2-(trimethylsilyl)ethoxy]methyl (SEM).

The term “silyloxy” as used herein means a silyl group, as definedherein, is appended to the parent molecule through an oxygen atom.

The definition of each expression, e.g., alkyl, m, n, and the like, whenit occurs more than once in any structure, is intended to be independentof its definition elsewhere in the same structure.

The abbreviations Me, Et, Ph, Tf, Nf, Ts, and Ms represent methyl,ethyl, phenyl, trifluoromethanesulfonyl, nonafluorobutanesulfonyl,p-toluenesulfonyl and methanesulfonyl, respectively. A morecomprehensive list of the abbreviations utilized by organic chemists ofordinary skill in the art appears in the first issue of each volume ofthe Journal of Organic Chemistry; this list is typically presented in atable entitled Standard List of Abbreviations.

Certain compounds contained in compositions of the present invention mayexist in particular geometric or stereoisomeric forms. In addition,polymers of the present invention may also be optically active. Thepresent invention contemplates all such compounds, including cis- andtrans-isomers, R- and S-enantiomers, diastereomers, (D)-isomers,(L)-isomers, the racemic mixtures thereof, and other mixtures thereof,as falling within the scope of the invention. Additional asymmetriccarbon atoms may be present in a substituent such as an alkyl group. Allsuch isomers, as well as mixtures thereof, are intended to be includedin this invention.

If, for instance, a particular enantiomer of compound of the presentinvention is desired, it may be prepared by asymmetric synthesis, or byderivation with a chiral auxiliary, where the resulting diastereomericmixture is separated and the auxiliary group cleaved to provide the puredesired enantiomers. Alternatively, where the molecule contains a basicfunctional group, such as amino, or an acidic functional group, such ascarboxyl, diastereomeric salts are formed with an appropriateoptically-active acid or base, followed by resolution of thediastereomers thus formed by fractional crystallization orchromatographic means well known in the art, and subsequent recovery ofthe pure enantiomers. A description of cavitand stereochemistry may befound in FIG. 12.

It will be understood that “substitution” or “substituted with” includesthe implicit proviso that such substitution is in accordance withpermitted valence of the substituted atom and the substituent, and thatthe substitution results in a stable compound, e.g., which does notspontaneously undergo transformation such as by rearrangement,cyclization, elimination, or other reaction.

The term “substituted” is also contemplated to include all permissiblesubstituents of organic compounds. In a broad aspect, the permissiblesubstituents include acyclic and cyclic, branched and unbranched,carbocyclic and heterocyclic, aromatic and nonaromatic substituents oforganic compounds. Illustrative substituents include, for example, thosedescribed herein above. The permissible substituents may be one or moreand the same or different for appropriate organic compounds. Forpurposes of this invention, the heteroatoms such as nitrogen may havehydrogen substituents and/or any permissible substituents of organiccompounds described herein which satisfy the valences of theheteroatoms. This invention is not intended to be limited in any mannerby the permissible substituents of organic compounds.

As used herein, “amine” refers to organic compounds and functionalgroups that contain a basic nitrogen atom with a lone electron pair.Amines are derivatives of ammonia, wherein one or more hydrogen atomshave been replaced by a substituent such as, for example, an alkyl oraryl group. As used herein, the term “amine” also includes amino acids.

As used herein, “void,” “voids,” or “void spaces” refers to spaceswithin the crystalline cavitand compositions of the invention, and maybe read to encompass terms of art including, but not limited to“cavities,” “microcavities,” “ultramicrocavities” “pores,” and“micropores.” For example, the void spaces may encompass one or moreguest molecules or they may be empty.

As used herein, “thermogravimetric analysis” or “thermal gravimetricanalysis” (TGA) is a method of thermal analysis in which changes inphysical and chemical properties of materials are measured as a functionof increasing temperature (with constant heating rate), or as a functionof time (with constant temperature and/or constant mass loss). In thepresent invention, TGA may be used to determine whether a cavitandcomposition of the invention is free of molecules or atoms in the voidspaces.

As used herein, “Standard conditions for temperature and pressure,”“standard temperature and pressure,” or “STP” are standard sets ofconditions for experimental measurements established to allowcomparisons to be made between different sets of data. The most usedstandards are those of the International Union of Pure and AppliedChemistry (IUPAC) and the National Institute of Standards and Technology(NIST), although these are not universally accepted standards. Otherorganizations have established a variety of alternative definitions fortheir standard reference conditions.

For example, in chemistry, IUPAC established standard temperature andpressure (informally abbreviated as STP) as a temperature of 273.15° K(0° C., 32° F.) and an absolute pressure of 100 kPa (14.504 psi, 0.986atm, 1 bar). An unofficial, but commonly used, standard is standardambient temperature and pressure (SATP) as a temperature of 298.15° K(25° C., 77° F.) and an absolute pressure of 100 kPa (14.504 psi, 0.986atm).

NIST uses a temperature of 20° C. (293.15 K, 68° F.) and an absolutepressure of 101.325 kPa (14.696 psi, 1 atm). The International StandardMetric Conditions for natural gas and similar fluids are 288.15 K(59.00° F.; 15.00° C.) and 101.325 kPa.

In certain embodiments, the cavitand compositions of the presentinvention are free of conventional solvent molecules, where conventionalsolvents are limited to chemicals that are generally in a liquid phaseat standard temperature and pressure.

Solvents described herein, include, but are not limited to, pentane,petroleum ether, hexane, heptanes, diethyl amine, diethyl ether,triethyl amine, tert-butyl methyl ether, cyclohexane, tert-butylalcohol, isopropanol, acetonitrile, ethanol, acetone, methanol, methylisobutyl ketone, isobutyl alcohol, 1-propanol, methyl ethyl ketone,2-butanol, isoamyl alcohol, 1-butanol, diethyl ketone, 1-octanol,p-xylene, m-xylene, toluene, dimethoxyethane, benzene, butyl acetate,1-chlorobutane, tetrahydrofuran, ethyl acetate, o-xylene,hexamethylphosphorus triamide, 2-ethoxyethyl ether,N,N-dimethylacetamide, diethylene glycol dimethyl ether,N,N-dimethylformamide, 2-methoxyethanol, pyridine, propanoic acid,water, 2-methoxyethyl acetate, benzonitrile, 1-methyl-2-pyrrolidinone,hexamethylphosphoramide, 1,4-dioxane, acetic acid, acetic anhydride,dimethyl sulfoxide, chlorobenzene, deuterium oxide, ethylene glycol,diethylene glycol, propylene carbonate, formic acid, 1,2-dichloroethane,glycerin, carbon disulfide, 1,2-dichlorobenzene, methylene chloride,nitromethane, 2,2,2-trifluoroethanol, chloroform,1,1,2-trichlorotrifluoroethane, carbon tetrachloride, andtetrachloroethylene.

Examples of encapsulated guests in a cavitand composition of (R,R¹,Y)Me,H,SiMe₂ are provided in table 1 below, including the properties ofvolume (Å³) and boiling point (C.°) associated with these guestmolecules.

TABLE 1 Summary of compositional, structural, and thermal analysis datafor isostructural clathrates xguest@Me, H, SiMe₂ (x ≤ 1) andCH₃CCH@Me,H,SiMe₂•2CHCl₃, arranged by boiling point of the guest.T_(max) − Encapsulated bp V_(guest) Fractional Occupancy V_(cav)V_(cell) TGA wt T_(max) T_(bp) Guest (° C.) (Å³) SCXRD^(a) Day 0^(b,c)Day³ 7^(c,d) (Å³) PF_(cav) (Å³) wt %_(th) %_(exp) (° C.) (° C.) none n/an/a n/a n/a n/a 28 0 8230(10) 0 0 395(12)° n/a 28 0 8403(2) CH₄ −162  28nm^(e) trace 0 — — — — nm — — Ar −186  28 0.29(2)^(e) 0.29(2)^(e)0.27(2)^(d,e) 41 0.7 8225(1) 1.5 1.7 129 315 Kr −153  35 0.97^(e,f)0.82^(d,e,f) 9.8^(i) 9.5 139 292 0.54(3)^(e) 0.54(3)^(e,g)0.07(1)^(d,e,g) 62 0.56 8223(2) Xe −108  42 0.77(3)^(e) 0.94^(e,f)0.76^(e,f) 62 0.68 8252(1) 14.6^(i) 13.7 171 279 0.77(3)e0.79(2)^(d,e,g) C₂H₄ −104  40 0.41(4)^(e) 0.41(4)^(e,g) 0.43^(e,g) 650.62 8227(1) 1.5 1.0 nm nm 0.062(9) 0.037(1) C₂H₆ −89 45 0.72(2),0.62(1)^(e) 0.72(2)^(e,g) 0.74(2)^(d,e,g) 67 0.67 8236(1) 2.72.8 >129 >218 0.056(5) 0.055(4) HC°CH −84 34 nd 0.055(4) 0 nd nd nd ndnd nd nd CH₃F −78 32 0.80(4), 0.45(11)^(h) 0.51(5) 0.27(6) 51 0.638218(2) 3.4 3.5 203 281 CO₂  −78^(n) 32 0.46(6)^(e) 0.39^(e,f)0.35^(e,f) 61 0.5 8214(1) 2.6 2.2 109 187 0.46(8)^(e,g) 0.35(5)^(e,g)CH₃CH═CH₂ −48 57 0^(e) 0 0 — — — — — — — CH₃CH₂CH₃ −42 62 0^(e) 0 0 — —— — — — — CH₃Cl −24 44 0.90(4), 1.0^(j) 1.0 0.84 62 0.71 8280(2) 6.2^(i)6.4 233 257 CH₃OCH₃ −24 53 0.82(4)^(e) 0.40(2) 0.35(1) 80 0.66 8349(1)4.7 5.3 162 186 CH₃C°CH −23 51 1.03(2)^(k) 1.0^(k) 0 74 0.69 5003(2)^(k)nm^(k) nd^(k) <25 nm CH₃Br    4 49 0.91(4) nd nd 75 0.65 8307(2) 11.0nm^(l) 230 226 CH₃SH    6 46 0.83(4) nd nd 72 0.64 8278(1) nd nd nd ndCH₃CH₂Cl   12 61 0.95(1)^(e) 1.0 1.0 76 0.80 8446(1) 7.7^(i) 7.8 158 146CH₂Cl₂   40 59 0.85(1) nd nd 74 0.80 8378(1) 9.9^(i) 9.7 179 139 CH₃I  42 53 0.95(3) nd nd 77 0.69 8371(1) 15.6^(i) nm^(l) 210 168 MeOH   6537 0.67(8) nd nd 52 8230(1) 2.8 3.6 160 95 BrCH₂Cl   68 64 0.75 0.62^(a)nd 82 0.78 8404(1) 11.7 9.6 177 109 EtOH   78 54 0.13(4) nd nd nm nm8241(2) 0.8 trace nm nm CH₃CN   81 44 0.96(3) nd nd 64 0.69 8244(2) 5.0nm^(l) nm nm CH₂Br₂   97 69 0^(a) 0.09^(a) nd — — — 2.0 2.2 115 18NO₂CH₃ 101 51 0.95(2) nd nd 69 0.74 8277(2) 7.0 nm^(l) nm nm H₂O 100 180.29(2)/0.40(2)^(m) nd nd 28 0.65 8225(25) <0.5 trace nm nm I₂  113^(n)60 0.06(1) nd nd nm nm 8242(1) 2.3 2.4 nd nd SCXRD = single crystalX-ray diffraction. V_(guest) = guest volume. V_(cav) = cavity volumeestimated from SCRXD data (see Supporting Information). PF_(cav) =V_(guest)/V_(cav), the packing fraction of the guest within the cavity.V_(cell) = unit cell volume at 100 K as measured by SCXRD (esds >2 Å³correspond to data from multiple crystals). TGA = thermal gravimetricanalysis (5° C./min.). Wt % = theoretical (th) percent mass lossaccording to the SCXRD occupancy and experimentally observed (exp)percent mass loss. T_(max) = temperature of maximum rate of guest-loss(5° C./min. heating rate). T_(max) − T_(bp) = difference between thenormal boiling point of the included guest and T_(max). Nd = notdetermined. Nm = not meaningful. ^(a)Crystals grown at room temperaturedirectly from the included solvent (by evaporation) or from saturatedCHCl₃ solutions of Me, H, SiMe₂ that were treated with excess guest (forCH₃OH, CH₃CH₂OH, I₂), or saturated with the gas of interest at 1 atm orthe pressure indicated in footnote e. ^(b)Unless otherwise noted, bulkpowder samples were obtained by passing the the gas of interest (1 atm)through a chloroform solution of Me, H, SiMe₂ until dry. ^(c)Occupanciesdetermined by ¹H NMR spectroscopy unless otherwise noted; esds are fromthree experiments. ^(d)Occupancies after single crystals left for oneweek under ambient conditions, or as indicated as follows: (Kr, 11 days(TGA); Kr, 14 days at 100° C. (SCXRD); Xe, 19 days (TGA); Xe, 112 days(SCXRD); C₂H₆, 10 days (SCXRD); CO₂, 10 days (SCXRD). ^(e)Occupancydetemrined by SCXRD. Crystals grown at room temperature from dry CHCl₃under a pressure of gas (Ar ≤70 atm; Kr ≤70 atm; Xe ≤50 atm; C₂H₄ ≤45atm; C₂H₆ ≤40 atm; CO₂ ≤60 atm; CH₃OCH₃ ≤6 atm; CH₃CH₂Cl <2 atm;CH₃CH₂CH₃ >20 atm; CH₃CH═CH₂, >20 atm). ^(f)Occupancies est. by TGA.^(g)Occupancy determined by SCXRD at 100 K; the same crystal was used asfor the Day 0 data. ^(h)Crystal from the same batch preparation, butafter 146 days (CH₃F) or 112 days (Xe) at ambient conditions. ^(i)Basedupon 100% ocupancy. ^(j)Crystal from EtOAc solution. ^(k)Crystallizes asthe CH₃CCH@Me, H, SiMe₂•2CHCl₃ solvate, which loses gas at roomtemperature. ^(l)Host sublimation occurs concommitantly with guest loss.^(m)Partial hydrates obtained from CHCl₃ (0.22 eq.) or acetone (0.38eq.), or by room temperature rehydration of empty single crystals of Me,H, SiMe₂. ^(n)Sublimation temperature. ° T_(max)(esd) of Me,H,SiMe₂sublimation from empty or clathrate samples. The sublimation onsettemperature is ca. 310° C.

The compositions of the invention may be characterized by an ability todifferentially take up or form complexes with certain molecular oratomic guests in the void spaces of the crystals. The compositions ofthe present invention may be selective for the uptake of certainmolecules over others, particularly molecules that are normally in gasphase at standard temperature and pressure. In some embodiments, acomposition of the present invention is capable of selectively formingcomplexes with certain hydrocarbons and/or halogenated alkanes.

In certain embodiments, a composition of the invention may selectivelytake up 2-carbon hydrocarbon gases over 3-carbon hydrocarbon gases. Incertain embodiments, a composition of the invention may selectively takeup a 2-carbon hydrocarbon gas over another 2-carbon hydrocarbon gas. Incertain embodiments, a composition of the invention may selectively takeup a 1-carbon halogenated alkane over a 2-carbon halogenated alkane. Incertain embodiments, the compositions of the present invention willselectively take up one or more hydrocarbon gasses, wherein thehydrocarbons may have 1, 2, or 3 carbon atoms, over carbon dioxide. Incertain embodiments, the compositions of the present invention willselectively take up one or more hydrocarbon gasses, wherein thehydrocarbons may have 1, 2, or 3 carbon atoms, over dimethyl ether(DME). In other embodiments, the compositions of the present inventionare suitable for selectively taking up gas molecules that are present insolvents.

In an embodiment, a complex of the present invention selectively takesup ethane over propane. In another embodiment, a composition of thepresent invention selectively takes up chloromethane over chloroethane.In another embodiment, a composition of the present inventionselectively takes up chloromethane and/or chloroethane over dimethylether. In another embodiment, a complex of the present inventionselectively takes up ethane gas over ethylene gas.

The selectivity of the compositions towards taking up certain moleculesmay be expressed by a selectivity coefficient, K_(A:B). For any two gasguest molecules, A and B, the selectivity coefficient, K_(A:B) may be ofat least about 2, about 5, about 10, about 20, about 50, about 100,about 200, about 500, about 1000, about 2000, about 5000, or about10,000.

For the uptake of gas molecules, the compositions of the presentinvention may exhibit a selectivity coefficient for C₂ hydrocarbongasses over C₃ hydrocarbon gasses, or C₃ hydrocarbon gasses over C₂hydrocarbon gasses, of at least about 2, about 5, about 10, about 20,about 50, about 100, about 200, about 500, about 1000, about 2000, about5000, or about 10,000.

In other embodiments, the compositions of the present invention mayexhibit selectivity of chloromethane over chloroethane, or chloroethaneover chloromethane, of at least about 2, about 5, about 10, about 20,about 50, or about 100.

In another embodiment, the compositions of the present invention mayexhibit selectivity of chloromethane and/or chloroethane over dimethylether, or dimethyl ether over chloromethane and/or chloroethane, ofgreater than about 2, about 5, about 10, about 20, about 50, about 100,about 200, about 500, about 1000, about 2000, about 5000, or about10,000.

Synthesis of Cavitands of Formula (I)

In an embodiment, cavitand compositions comprising crystals of formula(I) may be synthesized by synthetic methods known to those of ordinaryskill in the art.

While the synthesis of cavitands was known in the art, methods ofsynthesizing crystalline cavitand compositions comprising compounds offormula (I), wherein the void spaces of the cavitands are empty isbelieved new to the present invention. Described herein are methods ofobtaining these empty void compositions.

In an embodiment of the invention, after workup and subsequentpurification of a cavitand of formula (I), the resulting solidcomposition of formula (I) may be sublimed at high temperature and lowpressure to give single crystals of empty cavitand.

Crystalline cavitand compositions of the invention may be analyzed bysingle crystal x-ray diffraction (SCXRD) at, for example, 100 and 298 K.Further analysis of this guest-free form of crystalline cavitandcompositions of formula (I) using the MSRoll subroutine (Connolly, M. L.J. Mol. Graph. 1993, 11, 139) in XSEED (Barbour, L. J. J. Supramol.Chem. 2001, 1, 181) may show empty cavities of varying volumes, asdescribed in the foregoing.

Table 2, below, contains data from a cavitand compositions of theinvention that have been synthesized and subjected to analysis describedherein. In general the compositions of the invention, including thosedescribed in table 2, may expand or contract depending on conditionssuch as temperature, pressure, and the degree of gas occupancy withincavitand compositions of the invention.

For the compositions described herein, the error associated with unitcell measurement to account for variations in the conditions andmeasurements is expected to be about ±3-5% for the lattice constants.

TABLE 2 Cavitand Composition Data Stereo Cavitand (R, R¹, Y) isomer NewComplexes a (Å) b (Å) c (Å) α (°) β (°) γ (°) V (Å³) T (K) H, H, CH₂rccc Sublimed/Empty - Pnma 10.0412(28) 19.5873(54) 13.1954(36) 90 90 902595.3(12) 100 (2) NO₂CH₃ - P2₁/m 7.3877(13) 18.8361(33) 10.3891(18) 90110.492(2) 90 1354.22 100(2) H, Me, CH₂ rccc (CH₂Cl)₂ - P2₁/c12.1885(17) 8.3899(12) 30.8472(42) 90 90.702(2) 90 3154.21 100(2)CH₂Br₂ - Pbcm 10.8853(17) 15.4820(24) 19.0058(30) 90 90 90 3202.98100(2) BrCH₂Cl - Pbcm 10.8698(9) 15.2856(13) 19.0701(16) 90 90 903168.52 100(2) CHCl₃ - P2₁/c 15.2685(12) 14.4825(12) 15.3771(12) 90106.082(1) 90 3267.21 100(2) 2EtOAc - P-1 10.6979(11) 10.7309(11)35.6025(41) 98.001(2) 92.791(2) 111.251(1) 3750.28 100(2) NO₂CH₃ - P-18.2141(151) 10.4728(196) 19.5942(366) 102.325(23) 90.018(24) 108.811(22)1554.42 100(2) Sublimed/Empty - C2/c 20.0002(13) 7.9569(5) 38.3855(28)90 103.469(1) 90 5940.6(7) 100(2) Sublimed/Empty - C2/c 20.0499(13)8.0240(5) 38.5526(25) 90 103.277(1) 90 6035.8(7) 298(2) PXRD patterns ofpropene, propane, CH₃Cl, CH₃CH₂Cl, DME H, Et, CH₂ rccc H, i-Bu, CH₂ rcccH, Ph, CH₂ rccc 2CH₃I - P2₁/c 22.3506(34) 10.7665(16) 21.6563(33) 90115.703(2) 90 4695.69 100(2) 2NO₂CH₃ - P2₁ 10.7171(22) 13.1962(27)16.4770(34) 90 104.321(4) 90 2257.85 100(2) Sublimed/Empty - P-110.8153(15) 20.5120(47) 21.1317(48) 91.117(3) 104.804(3) 102.495(3)4411.1(X) 100(2) H, Ph, CH₂ rctt H, 4-CF₃Ph, CH₂ rccc Sublimed/Empty -P1 10.7920(26) 13.9228(33) 18.8059(45) 97.069(4) 92.221(4) 110.743(30)2612.08 100(2) H, 4-MePh, CH₂ rccc Sublimed/Empty - I-4 41.2138(33)41.2138(33) 10.9003(12) 90 90 90 18515(3) 100(2) H, 3,5-F₂Ph, CH₂ rcccsublimed insert data! Me, 3,5-CF₃Ph, CH₂ rctt 4CHCl₃ - P2₁/c 24.6086(43)18.7299(33) 34.2758(59) 90 107.531(2) 90 15064.52 100(2)Sublimed/x(H₂O) - P2₁/c 18.6310(28) 15.2825(23) 23.0555(35) 90 94.661(2)90 6542.8(X) 100(2) Sublimed/Empty - P-1 11.9261(81) 14.8033(101)20.0334(137) 70.627(8) 83.137(9) 81.696(8) 3291.9(X) 100(2) Me, H, CH₂rccc CCl₄ - Pbca 17.8176(10) 19.5344(11) 39.3215(21) 90 90 90 13686.09100(2) 2NO₂CH₃ - P4nc 15.4840(14) 15.4840(14) 7.1541(6) 90 90 90 1715.23100(2) 2.5(p-xylene) - P-1 11.7994(11) 18.7618(18) 21.9151(21)111.616(1) 91.618(2) 91.271(2) 4505.76 100(2) Sublimed/Empty - Pnma10.2260(11) 19.2246(21) 14.6088(16) 90 90 90 2872.0(5) 100(2) Me, Me,CH₂ rccc Ether - P2₁/n 9.2578(4) 22.2474(10) 18.3674(9) 90 98.929(2) 903737.14 100(2) EtOAc - P2₁/n 9.4203(8) 21.9453(18) 18.3180(15) 9097.794(1) 90 3751.92 100(2) p-xylene - P2₁/n 9.7050(9) 21.0726(20)19.2831(18) 90 96.013(2) 90 3921.88 100(2) p-xylene•x(p-xylene) - R3m35.0045(35) 35.0045(35) 9.5239(10) 90 90 120 10106.32 100(2)Sublimed/Empty - Pnma 10.8582(16) 19.6218(29) 15.6399(23) 90 90 903332.2(9) 100(2) Me, Et, CH₂ rccc Et0Ac - Pnma 17.1572(15) 19.7201(17)12.0228(10) 90 90 90 4067.81 100(2) m-xylene - Pnma 17.4735(17)19.7666(19) 12.2970(12) 90 90 90 4247.28 100(2) NO₂CH₃ - Pnma17.5037(19) 19.6988(21) 11.9868(13) 90 90 90 4133.07 100(2)Sublimed/Empty - P2₁/c 11.8341(10) 24.0475(20) 14.0138(12) 90 110.772(1)90 3728.8(5) 100(2) Me, i-Bu, CH₂ rccc EtOAc - Pnma 10.5134(11)19.9360(20) 24.1453(25) 90 90 90 5060.74 100(2) Sublimed/Empty - Pbca21.9246(72) 17.8065(58) 23.3378(75) 90 90 90 9111.09 100(2)Sublimed/Empty - Pnma 19.3612(13) 19.2325(13) 12.9860(9) 90 90 904835.5(6) 100(2) 19.5969(22) 19.5240(22) 12.9603(14) 90 90 90 4958.7(10)298 Me, Ph, CH₂ rctt 3p-xylene - P-1 13.0968(12) 14.7232(13) 18.1206(16)78.969(1) 77.827(1) 77.702(1) 3297.74 100(2) Sublimed/Empty - P2₁/c14.3913(21) 19.8671(29) 17.1496(25) 90 110.850(2) 90 4582.2(12) 100(2)Me, 4-MePh, CH₂ rccc Sublimed - P-1 15.5154(11) 17.7460(13) 20.4372(15)109.577(1) 100.463(1) 94.401(1) 5155.85 100(2) Me, 4-MePh, CH₂ rcccSublimed - Tetragonal (Unit Cell) 22.34 22.34 41.93 90 90 90 20925100(2) Me, 4-MePh, CH₂ rctt NO₂, H, CH₂ rccc 2NO₂CH₃ - P2₁/c 12.2944(23)11.8264(22) 24.6129(46) 90 103.841(2) 90 3474.77 100(2) Br, Me, CH₂ rccc2CCl₄ - Pnma 23.4262(48) 14.1072(29) 13.1381(27) 90 90 90 4341.85 100(2)2EtOAc - P2₁/n 12.3385(15) 15.4284(19) 22.0928(27) 90 90.773(2) 904205.28 100(2) p-xylene - P2₁/n 9.7358(3) 21.2018(7) 19.3794(7) 9095.906(2) 90 3978.99 100(2) Sublimed/Empty - C2/m 19.0053(81)20.5047(89) 9.4568(59) 90 115.363(3) 90 3330(3) 100(2) H, H, SiMe₂ rccc0.97CH₃Br - P2₁/m 10.7771(3) 23.2733(8) 15.3035(5) 90 90.404(2) 903838.3(2) 100(2) 0.91CH₃Cl - P2₁/m 10.8232(11) 23.1753(24) 15.2837(16)90 90.427(2) 90 3833.5(7) 100(2) MeCN - P2₁/n 15.6147(18) 11.2042(13)22.6801(27) 90 107.620(1) 90 3781.7(8) 100(2) 0.19CH₃F - P2₁/n15.3018(13) 11.1458(9) 22.6486(19) 90 107.110(1) 90 3691.8(5) 100(2)0.94CH₃I - P2₁/m 10.7251(14) 23.3754(31) 15.3431(20) 90 90.370(2) 903846.5(9) 100(2) 0.03DME•0.10(H₂O) - P2₁/n 15.2936(12) 11.1450(9)22.6250(17) 90 107.052(1) 90 3686.84 100(2) NO₂CH₃ - P2₁/m 10.8730(8)23.1887(17) 15.2072(11) 90 90.395(1) 90 3834.11 100(2) 0.24(CH₃CCH) -P2₁/n 15.4271(16) 11.1810(11) 22.7033(23) 90 107.510(1) 90 3734.6(7)100(2) Empty - P2₁/n 15.2400(19) 11.1290(14) 22.6153(28) 90 107.000(2)90 3668.1(8) 100(2) Sublimed/x(H₂O) - P2₁/n 15.2737(24) 11.1575(18)22.6217(36) 90 107.084(2) 90 3685(1) 100(2) H, Me, SiMe₂ rccc3(CH₃COCH₃)•x(H₂O) - P-1 11.1287(3) 15.3438(4) 17.0364(5) 108.583(1)106.323(1) 90.359(1) 2631.54 100(2) 2(C₆H₆)•x(H₂O) - P2₁/n 11.1753(7)23.0596(15) 19.6234(12) 90 95.737(1) 90 5031.58 100(2) CH₃I•x(H₂O) [CH₃Ioutside] - P2₁/n 11.2542(6) 16.5477(9) 24.1753(13) 90 93.015(1) 904495.96 100(2) 0.82(CH₃Cl)•CHCl₃ - P2₁/m 10.1381(11) 20.1495(21)11.2593(12) 90 91.773(1) 90 2298.92 100(2) CH₃F•CHCl₃ - P2₁/m10.0930(17) 20.2481(34) 11.1542(19) 90 91.313(2) 90 2278.92 100(2)0.20(DME)•CHCl₃ - P2₁/m 10.0507(15) 20.2763(30) 11.1636(16) 90 91.495(2)90 2274.27 100(2) CH₃CCH•CHCl₃ - P2₁/m 10.2254(29) 20.1340(57)11.2366(32) 90 92.390(4) 90 2311.36 100(2) mesitylene•x(H₂O) - P2₁/c10.9613(9) 19.3023(16) 24.1861(21) 90 103.097(1) 90 4984.14 100(2)0.93(CH₃Cl)•0.5(C₁₀H₁₄) - P2₁/n 9.2535(9) 11.4711(11) 24.1032(23)76.462(1) 86.097(1) 68.991(1) 2321.71 100(2) 0.17(CH₃F) - P2₁/n12.5117(9) 21.4532(15) 16.3933(11) 90 105.677(1) 90 4236.5(5) 100(2)0.22(DME)•C₁₀H₁₄ - P2₁/m 11.2823(23) 18.3561(37) 12.4616(25) 9090.656(3) 90 2580.62 100(2) CH₃CCH•C₁₀H₁₄ - P2₁/m 11.2920(7) 18.2727(11)12.5036(7) 90 90.430(1) 90 2579.86 100(2) Sublimed, x(H₂O) - P2₁/n12.4947(8) 21.4728(14) 16.3608(11) 90 105.536(1) 90 4229.16 100(2)0.5(toluene)•x(H₂O) - Cmc2₁ 20.8478(65) 9.3670(29) 45.1885(14) 90 90 908824.47 100(2) H, i-Bu, SiMe₂ rccc Me, H, SiMe₂ rccc Empty - C2/c23.8783(24) 8.3377(9) 42.1053(43) 90 100.631(1) 90 8238.9(15) 100(2)23.9160(31) 8.4243(11) 42.4217(55) 90 100.521(2) 90 8403.2(19) 296(2)CH₃I - C2/c 23.7418(15) 8.3761(5) 42.6673(28) 90 99.403(1) 90 8371.0(9)100(2) CH₃Br - C2/c 23.7815(29) 8.3577(10) 42.3173(52) 90 98.998(2) 908307.4(17) 100(2) CH₃Cl - C2/c 23.8190(24) 8.3375(9) 42.2158(43) 9099.032(1) 90 8279.7(15) 100(2) 0.80(CH₃F) - C2/c 23.8281(25) 8.3065(9)42.1464(44) 90 99.653(1) 90 8223.8(15) 100(2) EtCl - C2/c 23.5981(20)8.4762(7) 42.8436(35) 90 99.750(1) 90 8445.9(12) 100(2) 0.74(BrCH₂Cl) -C2/c 23.7650(20) 8.4219(7) 42.7905(36) 90 101.108(1) 90 8403.9(12)100(2) 0.85(CH₂Cl₂) - C2/c 23.8439(22) 8.3749(8) 42.7877(39) 90101.337(1) 90 8377.6(13) 100(2) 0.82(DME) - C2/c 23.8115(22) 8.3707(8)42.6458(40) 90 100.829(1) 90 8348.7(14) 100(2) 0.83(CH₃SH) - C2/c23.8489(14) 8.3186(5) 42.2892(26) 90 99.377(1) 90 8277.6(9) 100(2)0.06(I₂) - C2/c 23.8600(12) 8.3389(4) 42.1352(22) 90 100.525(1) 908242.4(7) 100(2) 0.72(C₂H₆) - C2/c 23.7918(15) 8.3456(5) 42.2677(26) 9099.785(1) 90 8270.5(10) 100(2) 0.77(Xe) - C2/c 23.7847(20) 8.3252(7)42.2368(35) 90 99.359(1) 90 8252.1(12) 100(2) 0.41(C₂H₄) - C2/c23.8487(12) 8.3237(4) 42.0407(21) 90 99.880(1) 90 8226.6(7) 100(2)0.54(Kr) - C2/c 23.8156(27) 8.3314(10) 42.0998(48) 90 99.948(1) 908227.7(17) 100(2) 0.29(Ar) - C2/c 23.8429(12) 8.3337(4) 42.0738(22) 90100.309(1) 90 8225.1(7) 100(2) 0.46(CO₂) - C2/c 23.9014(24) 8.3164(8)41.9864(43) 90 100.205(1) 90 8213.8(14) 100(2) 0.26(CH₄) - C2/c23.934(13) 8.3621(45) 42.157(23) 90 100.501(6) 90 8296(8) 100(2) MeCN -C2/c 23.8211(29) 8.3280(12) 42.0611(62) 90 98.894(2) 90 8244(2) 100(2)NO₂CH₃ - C2/c 23.9220(31) 8.2830(11) 42.4669(54) 90 100.387(1) 908276.7(19) 100(2) 0.67(MeOH) - C2/c 23.9064(22) 8.3015(8) 42.1497(39) 90100.301(1) 90 8230.2(13) 100(2) 0.13(EtOH) - C2/c 23.8670(26) 8.3297(9)42.1428(46) 90 100.399(2) 90 8240.6(16) 100(2) empty - P-1 11.8168(8)12.4352(8) 28.3927(18) 96.443(1) 90.292(1) 91.446(1) 4144.3(5) 100(2)2CHCl₃•CH₃CCH - P2₁/n 11.6044(23) 18.0529(35) 24.1294(47) 90 98.247(2)90 5002.67 100(2) Me, Me, SiMe₂ rccc Sublimed/Empty - P2/n 22.7948(24)9.2086(10) 43.2150(45) 90 100.508(2) 90 8919.05 100(2) Me, Et, SiMe₂rccc x(H₂O) - P2₁/n 14.3462(22) 17.7706(27) 19.8442(30) 90 101.492(2) 904957.7(13) 100(2) H, Me, SiEt₂ rccc EtOAc•x(H₂O) - P-1 11.3409(14)13.7853(17) 18.6917(24) 80.679(2) 81.906(2) 67.770(2) 2659.17 100(2) Me,H, SiEt₂ rccc Me, Me, SiEt₂ rccc BrCH₂Cl•x(H₂O) - P-1 11.9231(15)12.5610(16) 18.6982(23) 109.099(2) 97.895(2) 94.984(2) 2595.00 100(2) H,H, Si(i-Pr)₂ rccc H, Me, Si(i-Pr)₂ rccc Me, H, Si(i-Pr)₂ rcccSublimed/Empty - I4 16.5767(15) 16.5767(15) 9.9147(9) 90 90 90 2724.4(4)100(2) Me, Me, Si(i-Pr)₂ rccc

EXAMPLES General Methods

All solvents were used as received from Fisher (Pittsburg, Pa.).Reagents were obtained from Acros (Pittsburgh, Pa.) or Aldrich(Milwaukee, Wis.) and were used without further purification.Chromatography was carried out on silica gel (32-64 μm) from SilicycleChemical Division.

Thermogravimetric Analysis and TGA-MS

Thermogravimetric analyses (TGA) were performed with a TA InstrumentsQ5000IR TGA. Unless otherwise indicated, samples were placed in platinumpans and heated at a rate of 5° C./min under a constant flow of dryhelium (10 mL/min.).

¹H Nuclear Magnetic Resonance (¹H NMR)

For the characterization of the compounds, ¹H (400 MHz) and ¹³C (100MHz) NMR spectra were carried out on a Varian 400-MR spectrometer at 9.4T. MestReNova version 5.2.5-4119 software was used for data analysis.Deuterated solvents were used as received from Cambridge IsotopeLaboratories, Inc. Unless otherwise noted, these spectra were obtainedat room temperature and chemical shifts given are based upon on theresidual solvent peaks. Splitting patterns are labeled as singlet (s),doublet (d), triplet (t) and broad (br.). Encapsulated species areindicated by preceding an @symbol.

Data Collection and Structure Determination

Single crystal X-ray diffraction data were collected at 100(2) K (orroom temperature, as indicated) on a Siemens SMART three-circle X-raydiffractometer equipped with an APEX II CCD detector (Bruker-AXS) and anOxford Cryosystems 700 Cryostream, using Mo Kα radiation (0.71073 Å).The crystal structures were solved by direct methods using SHELXS, andall structural refinements were conducted using SHELXL-97-2 (G. M.Sheldrick, Acta Cyst. 2008, A64, 112-122). All non-hydrogen atoms weremodeled with anisotropic displacement parameters. All hydrogen atomswere placed in calculated positions and were refined using a ridingmodel with coordinates and isotropic displacement parameters beingdependent upon the atom to which they are attached. The program X-Seed(Barbour, L. Supramol. Chem. 2001, 1, 189. http://x-seed.net) was usedas a graphical interface for the SHELX software suite and for thegeneration of figures.

Cavity Volumes

Cavity volumes are usually extracted from atomic coordinate data bycomputationally probing the cavity with a sphere of a defined proberadius. The volume of space that can be encompassed by rolling thesphere around the interior of the cavity is summed over all achievablepositions of the sphere. The atomic coordinates maybe provided bycomputational or experimental data. For structure of formula (Ia),crystal structure data were used with normalized C—H bond lengths of1.08 Å. Cavity volumes were calculated using the X-seed interface(Barbour, L. Supramol. Chem. 2001, 1, 189. http://x-seed.net) to MSRoll(Connolly, M. L. J. Mol. Graph. 1993, 11, 139.), employing the defaultvan der Waals atomic radii and a 1.4 Å probe radius.

Example 1a: Synthesis of Empty Crystalline Cavitand Compositions ofFormula (Ia)

The synthesis of a compound of formula (Ia) was originally performed byCram by an the acid-catalyzed condensation reaction between acetaldehydeand resorcinol is high yielding (Tunstad, L. M.; Tucker, J. A.;Dalcanale, E.; Weiser, J.; Bryant, J. A.; Sherman, J. C.; Helgeson, R.C.; Knobler, C. B.; Cram, D. J. J. Org. Chem. 1989, 54, 1305).

An alternate synthetic pathway in analogy to that used by Sherman et al.for intramolecular ring closing among all hydroxy functionalitiesprovides better yields after all necessary purification steps (Naumann,C.; Roman, E.; Peinador, C.; Ren, T.; Patrick, B. O.; Kaifer, A. E.;Sherman, J. C. Chem. Eur. J. 2001, 7, 1637).

After workup and subsequent purification of the cavitand of formula(Ia), the colorless solid was sublimed at high temperature and lowpressure to give single crystals of empty cavitand which were analyzedby single crystal x-ray diffraction (SCXRD) at 100 and 298 K. Furtheranalysis of this guest-free form using the MSRoll subroutine (Connolly,M. L. J. Mol. Graph. 1993, 11, 139) in XSEED (Barbour, L. J. J.Supramol. Chem. 2001, 1, 181) showed a cavity volume of approximately 61Å³ using a 1.4 Å probe radius and normalizing all C—H bonds to 1.08 Å(FIG. 1).

Example 1b: X-Ray Analysis of Empty Cavitand Compositions of Formula(Ia)

The crystallographic parameters of a guest-free form of crystallineformula (Ia) are in congruence with the CH₂Cl₂@formula (Ia) solvate thatwas isolated and studied by Cram by SCXRD (FIG. 1) (the “@” symboldenotes that the cavitand encapsulates the guest) (Tunstad, L. M.;Tucker, J. A.; Dalcanale, E.; Weiser, J.; Bryant, J. A.; Sherman, J. C.;Helgeson, R. C.; Knobler, C. B.; Cram, D. J. J. Org. Chem. 1989, 54,130).

Powder x-ray diffraction analysis (PXRD) may also be used to analyzebulk samples of empty cavitand crystals and cavitand crystals, where thecavitand is complexed with a solvent guest. Differences in thecomposition may be observed by changes in shift and intensity of PXRDpeaks. This observation prompted further exploration of cavitandcomplexation with much more volatile gas species.

For cavitand compositions of formula (Ia), powder x-ray diffractionanalysis (PXRD) of the bulk samples of empty [a(simulated),b(experimental)] and the dichloromethane (DCM) complex [d(simulated),e(experimental)](FIG. 2) do, however, show a few differences: 1) theintensities of (11-2) and (11-3) are much larger for the DCM clathrateas opposed to empty due to the presence of chlorine atoms in the sample,2) a shift in the (200) peak to larger 2θ since the b axis is expandedto accommodate the large guest. This observation prompted furtherexploration of cavitand complexation with much more volatile gasspecies.

By utilizing a number of different guests, it is possible to probe acavities' ability to expand itself for guest accommodation, determinehow it behaves electronically upon complexation (dipolar interactions)as well as understand the stability these complexes may have over timeat ambient conditions and under elevated temperatures. Crystallographicdata for compositions of formula (Ia) are shown in table 3, below.

TABLE 3 Crystallographic Data for x(Guest)@formula (Ia). CH₂Cl₂@formulaBrCH₂Cl@formula CH₂Br₂@formula Crystal Parameters formula (Ia) formula(Ia) (Ia) (Ia) (Ia) Chemical formula C₃₆H₃₂O₈ C₃₆H₃₂O₈ C₃₇H₃₄O₈Cl₂C₃₇H₃₄O₈BrCl C₃₇H₃₄O₈Br₂ Formula weight, g/mol 592.62 592.62 677.58722.03 766.48 Growth solvent None None CH₂Cl₂ BrCH₂Cl CH₂Br₂ Crystalsystem Monoclinic Monoclinic Monoclinic Orthorhombic Orthorhombic Spacegroup C2/c C2/c C2/c Pbcm Pbcm Z 8 8 8 4 4 a, Å 20.0002(13) 20.0491(13)19.7686(29) 10.8698(9) 10.8853(17) b, Å 7.9569(5) 8.0236(5) 8.1693(12)15.2836(13) 15.4820(24) c, Å 38.3855(28) 38.5515(28) 38.9892(56)19.0701(16) 19.0058(30) α, deg 90 90 90 90 90 β, deg 103.469(1)103.281(1) 101.402(2) 90 90 γ, deg 90 90 90 90 90 V, Å³ 5940.6(7)6035.8(7) 6172.3(16) 3168.5(5) 50 ρ_(calc), g/cm³ 1.33 1.30 1.46 1.511.59 crystal dimensions, mm 0.38 × 0.26 × 0.16 0.38 × 0.26 × 0.16 0.45 ×0.28 × 0.28 0.64 × 0.42 × 0.35 1.30 × 0.92 × 0.44 T, K 100(2) 298(2)100(2) 100(2) 100(2) 2Θ max for refinement, deg 56.0 54.3 50.0 50.0 50.0total reflections 25444 25370 18834 22258 21936 independent reflections7093 6672 5439 2885 2909 no. of observed data 5407 4163 4036 2535 2128no. of parameters 392 401 428 228 228 μ, mm⁻¹ 0.093 0.092 0.267 1.4372.586 R_(int) 0.0362 0.0384 0.0504 0.025 0.0664 R₁(F), wR₂(F²), (I >2σ(I)) 0.0431, 0.1035 0.0453, 0.1034 0.0608, 0.1481 0.0404, 0.13110.0429, 0.1153 Goodness-of-fit on F² 1.058 0.997 1.054 1.219 1.069

Example 1c: Thermogravimetric Analysis of Empty Cavitand Compositions ofFormula (Ia)

The presence or absence of a guest molecule complexed within acrystalline cavitand composition of the invention can also be determinedby thermogravimetric analysis (TGA). TGA provides a tool to analyze thethermodynamics of guest loss upon heating of a composition up to thesublimation temperature of the cavitand composition.

In some instances, since the kinetics of guest loss are quite broad, anaccurate onset temperature cannot be ascertained; however the maximumrate of guest loss may be measured (T_(max)) and used as a quantitativemeasure of guest confinement.

A composition of formula (Ia) in the form of a dichloromethane solvatewas isolated after reaction purification and studied bythermogravimetric analysis (TGA), and then compared with other guestmolecule complexes, such as propene, dimethyl ether, andtrichloromethane (FIG. 3). The TGA values of several other guestmolecules are also summarized in Table 4, below.

For example, when a cavitand of formula (Ia) was complexed with thesolvent CH₂Cl₂ as the guest molecule, approximately one equivalent ofCH₂Cl₂ was lost (T_(max)=225° C.), an event that also coincided withsublimation of empty cavitand. Due to the large T_(ma) of guest loss forthis complex, the empty cavitand of formula (Ia) could not be generatedafter heating the sample at 220° C. for 3 days as the ¹H NMR stillshowed residual signals for the solvent.

To circumvent this shortcoming, a batch of CHCl₃@formula (Ia) crystalswere grown (by slow evaporation of a chloroform solution of formula(Ia)) and placed in the oven at 150° C. for 1 day to give the emptycavitand, as confirmed by ¹H NMR and powder x-ray diffraction (PXRD)(FIG. 2). The greater ease of guest loss in this case is due to a lesstightly packed phase of formula (Ia), an observation caused by thelarger van der Waals volume of chloroform over dichloromethane (74 vs.59 Å³).

Example 1d: Encapsulation Studies of Empty Cavitand Compositions ofFormula (Ia)

In order to study the selectivity of formula (Ia) for more volatileguests, a variety of gases were used that possess variable polaritiesand sizes (Table 4). Pure, empty formula (Ia) (25 mg) was placed in asealed borosilicate glass vial (when P_(vapor)<5 atm) or a Teflon bomb(when P_(vapor)>5 atm) along with enough liquefied gas to ensure anequilibrium between liquid and gas phases.

These mixtures were stirred for 1-2 days to ensure that all the emptymaterial dissolved in the liquefied gas before precipitating as theinclusion compound. The vessels were then opened and the remainingliquid was allowed to evaporate and a nitrogen stream was passed overthe solid for 20 minutes to remove residual gas. The solids were thenanalyzed by ¹H NMR, TGA and PXRD (FIG. 2) and the results summarized inTable 4.

TABLE 4 Complexes of formula (Ib) with various guests (bp, vdW volumes)and respective fractional occupancies as determined by ¹H NMR and TGA.Guest occupancies of gaseous species were also determined after ^(a) 8days and ^(b) 5 days by ¹H NMR. Fractional Occupancy bp Vol. TGA T_(max)T_(max) − T_(bp) Guest (° C.) (Å³) ¹H NMR wt %/eq. (° C.) (° C.) Propene−48 57 0.76(0.6)^(a) 6.6/0.99 187 235 Propane −42 62 0.03(0.03)^(a)1.5/0.20 75 117 CH₃Cl −24 44 1.00(0.80)^(a) 8.0/1.02 225 249 CH₃OCH₃ −2453 1.00(0.86)^(b) 7.1/0.98 103 127 EtCl 12 61 1.00(1.00)^(a) 9.7/0.99289 277 CH₂Cl₂ 40 59 1 13.9/1.13  225 185 BrCH₂Cl 68 64 1 18.7/1.05  10638 CHCl₃ 61 74 1 17.7/1.07  150 89 NO₂CH₃ 101 51 1 8.8/0.94 190 89

For example, chloromethane and chloroethane both have dipole moments,but different molecular geometries, yet both completely occupy thecavity of a compound of formula (Ib) as seen by ¹H NMR and TGA. As seenfrom the respective PXRD patterns, the (112) and (11-3) peaks areshifted towards lower 2θ values (FIG. 2).

This observation is even more pronounced in the case of chloroethane(Vol.=61 Å³); the empty crystalline cavitand complex of formula (Ia) hasa void space of 61 Å³, so the cell axes must swell in order to complexthe guest and still maintain the same packing motif as the empty cell.Also, since chloroethane fills virtually all the void space of thecavitand, it is more thermodynamically stabilized by van der Waalsinteractions, in addition to a quadrupole-dipole interaction among thephenyl rings. This increase in stability is seen in the higher T_(max)and T_(max)−T_(bp) value versus that of chloromethane [T_(max)—MeCl(255° C.) vs. EtCl (289° C.)/T_(max)−T_(bp)—MeCl (249° C.) vs. EtCl(277° C.)].

Analysis of CH₃OCH₃ complexes with a cavitand of formula (Ia) shows thatthe gas is fully occupied in the cavitand, however it is not 100%retained after 5 days. The T_(max)−T_(bp) value for this inclusioncomplex is also drastically diminished when compared to a guest ofsimilar van der Waals volume (EtCl). The reason for this is two-fold: 1)dimethyl ether does not possess a dipole, so the cavitand has less of anaffinity for the guest, and 2) the PXRD pattern of CH₃OCH₃ is notidentical to that of the empty cavitand of formula (Ia) and the EtClcomplex, suggesting that less efficient packing is responsible for thelack of gas confinement in the solid state.

Perhaps what is most intriguing is the selectivity that cavitand offormula (Ia) exhibits between propane and propylene. Propylene isproduced almost entirely as a byproduct of ethylene production bycracking and refinery processes (Propene. Ullmann's Encyclopedia ofIndustrial Chemistry, 7^(th) ed; VCH: Weinheim, Germany, 2005) and itsseparation from propane represents one of the most important operationsin the petrochemical industry. (Järvelin H.; Fair, J. R. Ind. Eng. Chem.Res. 1993, 32, 2201.)

Current methods for the separation of propane/propylene involve highlycomplex separation units and energy intensive processes due to theirsimilar properties and boiling points. Materials that have been shown toseparate such gases on a small scale include SBA-15 (Basaldella, E. I.;Tara, J. C.; Armenta, G. A.; Patifio-Iglesias, M. E.; Castellón, E. R.J. Sol.-Gel. Sci. Techn. 2006, 37, 141) and AgNO₃/SiO₂ sorbents (Rege,S. U.; Yang, R. T. Chem. Eng. Sci. 2002, 57, 1139).

Though the cavitand displays very low solubility in both liquefiedgases, the affinity that composition of formula (Ia) has for propyleneis unquestionable. The equivalents of propane that are bound arevariable since the ¹H NMR and TGA give distinctly different numbers(0.03 vs. 0.20 eq.). This may be due to propane being lost upondissolving the complex for NMR analysis. The low equivalents would alsoexplain how the PXRD pattern for the bulk sample is identical to that ofthe empty cavitand. Nonetheless, despite how little propane is presentin the cavity, it is held over a period of 8 days without any loss.

This behavior is the inverse to that of propylene. High equivalents ofpropylene found by ¹H NMR and TGA (nearly full occupancy), however itonly retains about 80% of the guest after 8 days. This observation isstill remarkable yet. The volume of propylene is only 5 Å³ less thanthat of propane, however is virtually fully occupied in the cavitand offormula (Ia). The lesser retention of propylene over time at ambientconditions is not surprising since it has a negligible dipole comparedto that of EtCl, which is retained 100% over 8 days. This is furtherillustrated by the different packing mode of the propylene complex asseen by the PXRD pattern; therefore not identical to the empty/DCMpattern. This feature of formula (Ia) may prove to be fruitful inindustrial applications towards the separation of propane and propylene.

Several single crystal structures of formula (Ia) in various solventswere also determined [NO₂CH₃, CHCl₃, CH₂Br₂, BrCH₂Cl, (CH₂Cl)₂]. In aneffort to determine the phases of CH₃CHCH₂@formula (Ib) andCH₃OCH₃@formula (Ib), the simulated PXRD patterns of all single crystalsolvates were superimposed (FIG. 2). Bromochloromethane (BCM) anddibromomethane (DBM) both crystallize in a primitive orthorhombiccrystal setting and do not compare with the gas solvates mentioned. Thedichloroethane and chloroform solvates of formula (Ia) crystallize in aprimitive monoclinic crystal setting and contain low 2θ planes that arenot congruent with the patterns of propylene and dimethyl ether boundcomplexes as well.

Example 2a: Empty Cavitand Compositions of Formula (Ib)

In another example, FIG. 4 shows the X-ray single crystal structure offreshly sublimed composition of formula (Ib) (100 K). The molecules packin an as-close-as-possible packed arrangement of cavitand layersadopting the monoclinic C2/c space group (Z=8) with a unit cell volumethat averages 8230(10) Å³ at 100 K, as determined for several crystals.

Though the molecules of formula (Ib) are close-packed, the bowl-shapedcavitands enforce discrete, empty cavities of approximately 28 Å³,constituting 2.7% of the crystal volume. Electron density analysisreveals that freshly prepared crystals are truly empty. Moreover,thermogravimetric analysis (TGA) of empty formula (Ib) reveals no massloss whatsoever up to the point of sublimation, which onsets at about310° C. and reaches its maximum rate at 395(12)° C. (heating rate=5°C./min.) (FIG. 5).

Example 2b: Guest Complexed Cavitand Compositions of Formula (Ib)

In contrast, when formula (Ib) is crystallized from certain smallmolecule solvents, it forms simple 1:1 solvent@formula (Ib) clathrates(e.g. solvent ═CH₃I, CH₃CN, NO₂CH₃, see Table 5) or partial solvates, asin xCH₂Cl₂@formula (Ib) (x≥0.85). Notably, the solvates adoptessentially the same crystal packing as the empty form, with thesolvents simply occupying the otherwise empty cavitand cavities. Forinstance, the 100 K unit cell volume of CH₃CN@formula (Ib)(V_(cell)=8244(2) Å³)—the clathrate of the smallest of these solvents—isnearly indistinguishable from empty formula (Ib), despite a doubling ofthe cavity volume (V_(cav)) from 28 Å³ to 64 Å³ (6.2% of the crystal) toaccommodate the 44 Å³ CH₃CN guest. The solvent is efficiently packedwithin the formula (Ib) cavity, occupying approximately 69% of theavailable volume.

Swelling of the formula (Ib) cavity largely entails an outward swingingof the O—Si—O linkages such that the angles between the planes definedby the O—Si—O linkages and the plane defined by the upper rim atoms ofthe pseudo 4-fold symmetric cavitand (angle τ) are all more acute (FIG.10). For CH₃CN@formula (Ib), the average τ angle is 8.40 smaller(Δτ(avg.)) than for the empty phase, despite little overall change inthe unit cell volume (Table 6). For clathrates of the other solvents,however, the unit cells are slightly expanded as compared to the emptyform.

The observed unit cell volumes, and conformational Δτ angles of the hostare loosely correlated with the volume of the solvent: the cavitandshows a modest ability to expand its molecular cavity, from 28 Å³ to anapparent maximum of about 80 Å³, to accommodate guests. Moreover, thecrystal packing of formula (Ib) shows some ability to accommodate modestprotrusions of the guests from the upper rim of the cavity via slightalterations of the crystal packing and expansion of the unit cell, up toabout 8440 Å³ (measured at 100 K).

For example, the 100 K unit cell of a single crystal of0.85CH₂Cl₂@formula (Ib) (V_(cell)=8378(1) Å³)—formally, this crystal isa solid solution of empty and occupied cavitands—is larger byΔV_(cell)=148 Å³ (1.8%) relative to empty formula (Ib). The degree ofcrystal expansion is minimal, however, considering that, on average perunit cell, 6.8 molecules of CH₂Cl₂ (6.8° 59 Å³=401 Å³, which require 558Å³ of space in pure crystalline CH₂Cl₂ at 153 K) have been introducedinto the material. In fact, the seemingly partial occupancy of CH₂Cl₂suggests that this guest approaches the upper volume limit of what canbe accommodated by the cavitand or its monoclinic empty-like phase.

TABLE 5 Calculations of the electron density in cavitand cavity usingSQUEEZE. A guest occupancy was calculated from the number of electronsfound and compared with that of the values obtained in the SHELXLatomistic refinement. Esds are calculated based upon occupancies derivedfrom SHELXL, SQUEEZE and individual occupancies. Squeeze Squeeze SCXRDAvg St. Dev. Individual Occupancies Guest (e−) (occ.) occ. Occ. Occ.Atom 1 Atom 2 Atom 3 None 1.63 0.163 0 0.08 0.12 CH₄ 2 0.25 0.26 0.260.01 Ar 5 0.28 0.31 0.29 0.02 Kr 20 0.56 0.52 0.54 0.03 Xe 41 0.75 0.790.77 0.03 C₂H₄ 6 0.38 0.44 0.41 0.04 0.45 0.43 C₂H₆ 13 0.72 0.71 0.720.02 0.71 0.74 CH₃F 14 0.83 0.77 0.80 0.04 0.79 0.75 CO₂ 10 0.45 0.460.46 0.06 0.53 0.38 0.44 CH₃Cl 23 0.92 0.87 0.90 0.03 0.91 0.86 CH₃Cl 251 1 1.00 0.02 0.99 0.97 CH₃OCH₃ 21 0.81 0.82 0.82 0.04 0.88 0.8 0.79CH₃CCH 23 1.05 1 1.03 0.02 1.03 1 1.02 CH₃Br 40 0.93 0.88 0.91 0.04 0.950.88 CH₃SH 22 0.85 0.8 0.83 0.04 0.87 0.79 EtCl 32 0.94 0.95 0.95 0.010.95 0.96 0.93 CH₂Cl₂ 36 0.86 0.84 0.85 0.01 0.85 0.86 0.84 CH₃I 61 0.980.92 0.95 0.03 0.96 0.92 MeOH 12 0.66 0.68 0.67 0.08 0.76 0.61 BrCH₂Cl45 0.75 0.75 0.75 0.00 0.48 0.67 1 EtOH 3 0.12 0.13 0.13 0.04 0.14 0.20.1 MeCN 20 0.95 0.97 0.96 0.03 0.98 0.99 1.02 CH₂Br₂ 3 0.04 0 0.02 0.03NO₂CH₃ 30 0.94 0.96 0.95 0.05 0.98 0.88 0.95/0.98 (0.29)H₂O 3 0.3 0.280.29 0.01 (0.21)H₂O 1.75 0.18 0.21 0.20 0.02 I₂ 7 0.066 0.06 0.06 0.010.07 0.06

TABLE 6 Angles, τ, between planes of all O—Si—O functionalities and theplane defined by the upper rim carbon atoms of the arene rings offormula (Ib) (see FIG. 10 for definition of τ). Angle (Small to large)Avg. St. Δτ Guest 1 2 3 4 (T) Dev. (°) V_(g) V_(cell) None 74.16 81.3388.69 88.77 85.01 5.20 0 8230 Ar 73.23 81.03 87.41 89.61 82.82 7.36 2.228 8225 Kr 72.42 80.45 85.67 87.66 81.55 6.80 3.5 35 8223 Xe 69.53 78.6181.37 83.26 78.19 6.08 6.8 42 8252 C₂H₄ 70.86 80.43 85.28 88.08 81.167.56 3.8 40 8227 C₂H₆ 65.6 79.19 81.38 85.20 77.84 8.53 7.2 45 8236 CH₃F71.37 79.7 84.23 86.06 80.34 6.55 4.7 32 8218 CO₂ 68.79 81.25 86 89.5181.39 9.05 3.6 32 8214 CH₃Cl 66.45 78.72 78.89 83.04 76.78 7.17 8.2 448280 CH₃OCH₃ 58.1 76.9 82.08 83.70 75.20 11.76 9.8 53 8349 CH₃CCH 74.2574.31 77.16 80.79 76.63 3.09 8.4 51 CH₃Br 63.36 77.04 78.17 81.71 75.078.06 9.9 49 8307 CH₃SH 63.63 77.9 78.43 84.05 76.00 8.71 9.0 46 8278EtCl 61.46 75.8 78.93 80.20 74.10 8.63 10.9 61 8446 CH₂Cl₂ 56.64 73.681.73 82.92 73.72 12.12 11.3 59 8378 CH₃I 55.88 75.96 77.21 78.76 71.9510.78 13.1 53 8371 MeOH 69.91 78.37 85.3 87.76 80.34 8.01 4.7 37 8230ClCH₂Br 57.27 73.81 82.01 83.29 74.10 11.98 10.9 64 8404 EtOH 72.3280.86 87.5 89.94 82.66 7.89 2.4 54 8241 MeCN 64.54 78.94 79.01 83.9476.61 8.38 8.4 44 8244 NO₂Me 60.62 72.08 81.19 82.52 74.10 10.12 10.9 518277 H₂O 74.43 81.42 88.6 89.22 83.42 6.96 1.6 18 8225 I₂ 72.91 80.788.18 89.68 82.87 7.71 2.1 60 8242

The aforementioned behavior-namely, the ultramicrocavity structure ofempty formula (Ib), the isotructural and volume and/or shape-selectivenature of its solvates, and the ability of the hydrophobic cavity toscavenge water from certain organic solvents-prompted an exploration ofthe potential for formula (Ib) to selectively capture and confine gasesduring the process of crystal growth. The following paragraphs detailvarious experiments conducted and observations made toward this end.

Example 3: Gas Complexed Cavitand Compositions of Formula (Ib)

To initially probe the ability of formula (Ib) to form stable gasclathrates, chloroform solutions of formula (Ib) were treated by passingvarious protic gases (CH₃CH₂Cl, CH₃OCH₃ CH₃CH₂CH₃, CH₃CH═CH₂, CH₃C≡CH,CH₃Cl, CH₃F, CH₃CH₃, CH₂═CH₂, CH₄) through them until the solvent hadcompletely evaporated. The resulting solids were then rigorously flushedwith nitrogen and were subsequently analyzed by ¹H NMR spectroscopy. Thespectra showed unequivocally that exactly one equivalent ofchloroethane, chloromethane, and propyne were captured by the cavitandunder these conditions whereas lesser, but significant, amounts offluoromethane (0.51(3) equivalents) and dimethylether (0.40(2)equivalents) were captured, and very small amounts of ethane (0.056(5)equivalents), ethylene (0.062(9) equivalents), acetylene (0.055(4)equivalents), and possibly methane (trace) were captured.

Notably, there was no evidence for the capture of propane or propeneunder these conditions. As a preliminary probe of the kinetic stabilityof these gas clathrates, the resulting solids were reanalyzed afterseven days exposure to room temperature conditions in open vials; theresults showed that, with the exception of methane, acetylene, andpropyne, even extremely volatile gases such as CH₃F (b.p.=−78° C.) andethane (b.p.=−89° C.) are largely or completely retained by the hostafter one week. Notably, propyne, for which exactly one equivalent iscaptured by formula (Ib) initially, was completely missing from thesolid after 7 days, an observation seemingly at odds with the observedconfinement of much more volatile and less effectively captured gases.

The initial gas occupancy trends observed in the above experiments canbe explained as follows. The small cavity of formula (Ib) is able tobind the gases to varying degrees in CHCl₃ solution, a solvent which istoo large to compete for the cavity. Binding of gases and other smallmolecules by cavitands in solution is not new: Cram and coworkersobserved that the related, more shallow-bowled cavitand (R, R¹, Y)H,Me,SiMe₂ weakly bind CS₂, CH₃CCH, and even O₂ in CHCl₃ solution,though the association constant measured for CS₂ (the only one measured)was very small (K_(a)=0.22 at 300 K).

Thus, enclathration of the halomethanes can be attributed to their smallsize, linear shape, and complementary host-guest dipole-dipoleinteractions, with CH₃Cl and CH₃Br being bound more effectively thanCH₃F, likely for entropic reasons. Similarly, due to its complementary,linear shape and dipolar nature, one equivalent of propyne is capturedby formula (Ib), though propyne is lost from the resulting solid muchmore rapidly than are the other gases.

Notably, despite attempts to observe it, Cram and coworkers found noevidence for the complexation of CH₃I by H,Me,SiMe₂ in CHCl₃, or, forthat matter, CH₂Cl₂, H₂O or CO₂. Nonetheless, we find that each of theseguests is enclathrated by formula (Ib) when crystallized under theappropriate conditions (vide infra). When a series of non-linear gasesof nearly identical size and shape are compared, the xguest@formula (Ib)occupancies follow the trend: chloroethane>dimethyl ether>>propane,propene (completely excluded). These occupancies can also generally beexplained on the basis of host-guest dipole-dipole interactions.

Most interesting, however, is the ability of formula (Ib) to capture andretain small amounts of the highly volatile C₂ hydrocarbons (ethane,ethylene, acetylene) as compared to its complete exclusion of the lessvolatile C₃ hydrocarbons propane and propene. One might expect a greaterdispersion interaction between the higher surface area propane/propeneand the host as compared to the C₂ hydrocarbons, but without being boundby theory, the former may be either: i) too large or inappropriatelyshaped to be accommodated by molecular cavity of the host in solution,or ii) excluded from the crystal during the process of crystalnucleation and growth, which is capable of placing further threedimensional constraints on the open-ended host cavity if the complex isto pack in the low-energy, empty-like monoclinic arrangement.Apparently, bent small molecules such as methylene chloride andchloroethane are only be taken by formula (Ib) because they offer asignificant dipole to compensate for the stresses associated with theirincorporation into the necessarily expanded molecular cavity.

To probe the structural factors at play with respect to enclathrationselectivity, and to extend the investigation to non-protic gases andother small molecule guests (e.g. antisolvents), the X-ray crystalstructures of numerous isostructural xguest@formula (Ib) (x≤1)clathrates were obtained. FIG. 6 depicts thermal ellipsoid plots andsome pertinent structural indicators regarding many of the guest@formula(Ib) complexes. In all cases, the guest occupancies were estimated bysingle crystal X-ray diffraction experiments, and TGA and ¹H NMRobtained on the bulk samples are generally in accord with the X-rayresults (with specific exceptions; see Supporting Information).Moreover, the X-ray structures of these isostructural gas clathrates areof such quality that one can place some confidence (est.±3%) in theprecision of the guest occupancies as determined by refinement of thediffraction data.

When nearly saturated chloroform solutions of formula (Ib) were brieflysaturated with one atmosphere of the following gases, followed bycapping of the flasks, x(gas)@formula (Ib) (x≤1) complexes precipitatedas large single crystals over a period of hours to days: CH₃F(x=0.80(4)), CH₃Cl (x=0.90(4)), CH₃Br (x=0.91(4)), CH₃SH (x=0.83(4)).That simply exposing solutions to one atmosphere of these gases inducescrystallization of the gas clathrate from an otherwise unsaturatedsolution of formula (Ib) is significant. The lattice energy of thegas@formula (Ib) complexes is lower than that of the isostructural emptyor partial hydrate phases. Thus, the observation of precipitation, andthe occupancy of the resulting clathrate obtained under similarconditions is a semi-quantitative indicator of the extent of gascomplexation in solution and/or the selectivity of the crystallizationprocess.

For example, when solutions were similarly treated with non-polar gasessuch as ethane, ethylene, acetylene, carbon dioxide, dimethyl ether, orthe Noble gases, either no precipitates formed, or crystals formed thatwere found by X-ray diffraction to be simple partial hydrates orseemingly very low occupancy complexes (<5%). Nonetheless, crystals ofeach of these gas clathrates could be obtained (except acetylene), andtheir structures determined, simply by growing crystals from chloroformsolutions that were pressurized with the gas.

Generally, the increased solution concentration of the gas underpressurized conditions pushes the solution binding equilibrium towardcomplexed species, and the gas occupancy of the resulting precipitate isultimately a factor of the gas pressure, the equilibrium constant forgas complexation in solution, and the selectivity of the crystallizationprocess with respect to incorporation of empty or occupied molecules offormula (Ib). Certain gases required only low pressures to observesignificantly occupied crystals—e.g., single crystals of0.82CH₃OCH₃@formula (Ib) were obtained at pressures less than the gasvapor pressure of 6 atm—whereas others required high pressures to obtaineven low occupancy crystals.

For example, crystals of 0.29Ar@formula (Ib) were obtained by sealing avial containing formula (Ib) in CHCl₃ (with 3 Å molecular sieves) withliquid argon in a 23 mL teflon-lined digestion bomb and allowing thesystem to equilibrate at room temperature for several days; theequilibrium pressure under these conditions was not measured, but wasestimated, P(est.), to be necessarily less than 70 atm.

Similarly, high pressures were required for even modest uptake of CO₂,but the atomic-resolution crystal structure of 0.46CO₂@formula (Ib)could nonetheless be obtained. Crystals grown under high pressures ofmethane (P(est.)<60 atm) contained only trace amounts of methane (by ¹HNMR and TGA) and the resulting single crystal structure of the putativemethane clathrate was not formally distinguishable from the partialhydrate. Notably, experiments were unable to prepare formula (Ib)clathrates of propane or propene even under pressurized conditions.

The numerous single crystal structure determinations ofx(gas/guest)@formula (Ib) (x≤1) clathrates constitute an unusual exampleof a systematic, sub-angstrom resolution exploration of the structuralcharacteristics of small, semi-flexible nanospaces in response tomolecular probes (see FIG. 6) and sheds light on structure-selectivityand structure-stability relationships in ultramicrocavity materials.Moreover, the existence of kinetically stable (vide infra) gasclathrates of formula (Ib) also provides a means to study the structureand properties of gas molecules in a highly confined environment.

It is believed that the structure determination of 0.80(4)CH₃F@formula(Ib) constitutes the first single crystal structure determination of thefluoromethane molecule (Freon 41), the determined C—F bond length(1.391(4) Å) being in accord with theory (or other experiments?1.39(x)Å). Similarly, the CSD contains only one atomic-resolution structurecontaining an ordered, uncoordinated ethylene molecule—pure ethylene at85 K—and only two examples of ordered ethane—a twinned ethane crystal at85 K and a twinned crystal of the C₂H₆@C₆₀ clathrate, anotherultramicrocavity clathrate.

Some telling structural features are immediately apparent. First, thesmaller, less polar, and lighter gases enclathrated by formula (Ib)(e.g. CO₂, CH₃CH₃, H₂C═CH₂, CH₃F) exhibit a greater degree of thermalmotion at 100 K than do the larger, more polar, and heavier moleculesbound in the xguest@formula (Ib) phase. For instance, while CH₃Fexhibits larger thermal parameters than the larger and heavier CH₃Cl,CH₃F is clearly more fixed by the formula (Ib) cavity at 100 K than thelarger, similar mass ethane molecule, or the heavier CO₂ molecule. Theeffect is a manifestation of the enthalpy-entropy interplay insupramolecular systems. Regardless, each of these volatile gases isfound to be generally ordered within the cavity at 100 K and can berefined without restraints. For instance, the freely refined ethane C—Cbond and ethylene C═C bond lengths in 0.72(2)CH₃CH₃@formula (Ib) and0.41(4)C₂H₄@formula (Ib) are 1.50(x) Å and 1.34(x) Å, respectively, theformer value suggesting some degree of librational shortening.

The occupancies of the x(gas)@formula (Ib) (x≤1) clathrates obtainedunder the various preparation conditions, and the apparent strainedconditions of certain larger-volume gas clathrates, suggestopportunities to apply formula (Ib) toward the separation of gases.

For instance, the non-cryogenic separation of xenon and krypton (andkrypton sequestration) remains an important problem. Formula (Ib) takesmore xenon than krypton at similar pressures, a trend that is in linewith their chloroform solubilities and polarizabilities and thepreferences of most microporous materials that are capable ofaccommodating xenon.

Perhaps more interesting is the fact that formula (Ib) takes uphydrocarbons with a preferential order of ethane>ethylene>>methane withcomplete exclusion of propane and propene. And the apparentethane>ethylene clathrate stability order is a reversal of thethermodynamic selectivity observed by most zeolitic and Lewis acidicsorbents. A particularly exceptional manifestation of gas-selectiveenclathration by formula (Ib) was uncovered in experiments designed togrow single crystals of the chloroethane clathrate.

Example 4: Separation of Chloromethane and Chloroethane by CavitandCompositions of Formula (Ib)

When a large excess of 99.7% purity chloroethane gas was passed throughchloroform solutions of pure formula (Ib), the initial precipitate issingle crystals of the chloromethane clathrate, CH₃Cl@formula (Ib),instead of the expected CH₃CH₂Cl@formula (Ib) clathrate. Analysis of theoriginal chloroethane gas sample by ¹H NMR spectroscopy revealed it toconsist of an approximate 1477:1 ratio of CH₃CH₂Cl to CH₃Cl. When thenear-pure gas is passed through a concentrated CDCl₃ solution of formula(Ib), however, ¹H NMR spectroscopy of the solution reveals that thecavitand serves to hold and thereby concentrate the CH₃Cl in the solventover time, effectively removing the CH₃Cl from the CH₃CH₃Cl stream, nodoubt via selective complexation. Single crystals of the chloroethaneclathrate, CH₃CH₂Cl@formula (Ib), had to be obtained by limiting theamount of CH₃Cl available to the cavitand, treating a chloroformsolution of formula (Ib) with a small volume of liquefied chloroethaneunder pressurized conditions.

Formula (Ib) also has utility in another gas separation of industrialsignificance, namely the separation of dimethyl ether and chloromethane.These gases, with identical boiling points (−24° C.), inevitably appearas mixture during the industrial synthesis of chloromethane by theaction of hydrochloric acid on methanol. As the mixture cannot beseparated by distillation, current methods of separation resort toaqueous liquid-liquid extraction or the wasteful destruction of CH₃OCH₃by acids. Dimethyl ether is less readily included into formula (Ib) thanchloromethane and forms a clearly more strained gas clathrate. As apreliminary test of the feasibility of using formula (Ib) for thisseparation, a pressurized, liquid, 9:1 mixture of CH₃OCH₃:CH₃Cl wasslurried with 0.1 equivalents of formula (Ib) at room temperature andthe liquid was allowed to evaporate. The resulting solid contained a X:Yratio of CH₃Cl:CH₃OCH₃, yielding a selectivity coefficient of ca. 47.

Example 5: Kinetic Stability of Gas Complexed Cavitand Compositions ofFormula (Ib)

The x(gas)@formula (Ib) (x≤1) clathrates exhibit a remarkable kineticstability. In general, heating above 100° C. is required to remove thegases from the material at a reasonable rate. For example, despite thelow normal boiling points of many of the guests, the x(gas)@formula (Ib)crystals do not require any special handling and show no sign of gasloss at room temperature on a timescale of hours to months, dependingupon the identity of the confined gas. As a probe of their stability,single crystals of x(gas)@formula (Ib) clathrates of the most volatileguests—x(gas)=0.29(2)Ar, 0.77(3)Xe, 0.41(4)C₂H₄, 0.72(2)C₂H₆,0.46(6)CO₂, 0.80(4)CH₃F—were kept under ambient conditions and wereagain analyzed by single crystal X-ray diffraction after 7, 112, 7, 10,10, and 146 days, respectively (the x(CH₃F)@formula (Ib) crystal was adifferent crystal in the second structure determination, though acrystal from the same original batch preparation was chosen foranalysis). None of the crystals lost their transparency or showedsignificantly diminished single crystal diffraction intensities overthis time frame. With the exception of the x(CH₃F)@formula (Ib) andx(CO₂@formula (Ib) crystals, which gave refined occupancies ofx=0.45(11) and 0.35(5) after 146 and 10 days at room temperature,respectively, the occupancies of the other aforementioned x(gas)@formula(Ib) clathrates were identical within the estimated precision of thesingle crystal measurement (ca.+/−3-5%).

As an additional measure, the single crystal of 0.45(11)CH₃F@formula(Ib) was heated at 150° C. for four days; redetermination of thestructure of this crystal gave a refined occupancy of 0.23(5) for theCH₃F species. Further heating for several days at 190° C. finallyemptied the crystal entirely. Similarly, numerous single crystals of thexH₂O@formula (Ib) (x≤0.30) partial hydrates could be dehydrated, also ina single crystal to single crystal fashion, by heating at 150° C. Andafter ten days in the oven at 100° C., the original single crystal of0.54(3)Kr@formula (Ib) gave a single crystal that was determined to be0.07(x)Kr@formula (Ib). In general, it was found that single crystals ofthe x(gas)@formula (Ib) clathrates could be readily degassed at hightemperatures while preserving single crystallinity if their unit cellvolumes did not appreciably contract upon emptying. Single crystalclathrates of the larger volume guests (e.g. CH₂Cl₂, Xe), however,tended to fracture under the stresses of degassing and/or non-uniformcontraction upon high temperature guest loss.

TGA of the bulk x(gas)@formula (Ib) samples further underscores thekinetic stability of the x(gas)@formula (Ib) clathrates. FIG. 7 shows,for example, the TGA behavior (5° C./min.) of four selected clathrates.Though the onset temperatures for gas loss are difficult to define dueto the very slow release rates below 100° C., experiments found that theT_(max) values, the temperature that defines the maximum rate of massloss, are fairly reproducible (+/−5° C.) for powdered samples and serveas a practical indicator of the relative kinetic stability of theclathrates.

Moreover, the parameter T_(max)−T_(bp), where T_(bp) is the normalboiling point of the gas, is a useful indicator of the extent to which amaterial is capable of kinetically confining an otherwise volatile gas.For example, the T_(max) values of the gas clathrates in FIG. 7 followthe order: CO₂<Ar<Kr<Xe. Though the T_(max) values of this seriescorrelate with the kinetic diameters of these gases, this behavior isnot general. For example, the T_(ma) of the chloroethane and dimethylether clathrates similar since b4 and after structure ˜same, T_(max)reflective of diffusion rate through crystal.

The cavitand formula (Ib) was shown to bind a variety of gases underambient conditions and at elevated pressures, including chloromethane,chloroethane and dimethyl ether (DME) (Table 7).

TABLE 7 Summary data for chloromethane, chloroethane and dimethyl etherBoiling Density Gas MW (g/mol) point (° C.) Vol. (Å³) (g/mL) MeCl 50.49−23.9 44 0.92 (20° C.) EtCl 64.52 12.3 61 0.924 (0° C.) DME 46.07 −24.853 0.67 (20° C.)

While attempting to grow a crystalline solvate of EtCl@formula (Ib) (the“@” symbol denotes the cavitand encapsulates the guest) by bubbling EtClgas into a saturated solution of formula (Ib) in chloroform, the singlecrystals that formed contained virtually no EtCl, but MeCl instead. Thiswas due to the cavitand's selectivity of MeCl vs. EtCl; the bulk gascontained a ratio of 1:1460, however when the gas was bubbled throughthe solution of cavitand, this ratio changed to 1:91. This prompted usto further probe the selectivity of this cavitand towards chloromethane.

Example 6: Separation of Chloromethane and Chloroethane from DimethylEther by Cavitand Compositions of Formula (Ib)

Chloromethane is mainly produced commercially by the hydrochlorinationof methanol, a process that is much more practical than the traditionalmethane chlorination method (Chlorinated Hydrocarbons. Ullmann'sEncyclopedia of Industrial Chemistry, 7^(th) ed; VCH: Weinheim, Germany,2005). Synthesis is carried out in the gas phase under activated Al₂O₃with excess hydrogen chloride, to drive the equilibrium towards MeClformation, while reducing the amount of dimethyl ether side productformed (0.2 to 1%). The residual DME is then destroyed during the MeClpurification process by passing the gaseous mixture through a 96%sulfuric acid column, forming methyl sulfate and ‘onium salts’.Treatment of dimethyl ether with HCl (U.S. Pat. No. 3,981,938) or SbCl₃(DE 2640852) back towards MeCl formation has been reported.

By utilizing the selective nature of the cavitand, methods for thedestruction of side products such as DME or meticulous separations ofchloroalkanes can be avoided entirely. Separation experiments that arebased on selectivity of one guest over another require an inclusionpreference of the host. Pairwise experiments that utilize the host andare run in the presence of both guests with known mole fractions can beused to determine the selectivity coefficient of the host (K_(A:B)).K _(A:B)=(K _(B:A))⁻¹ =Y _(A) /Y _(B) ·X _(B) /X _(A)  [1]

As defined by Pivovar et al., equation [1] shows the selectivitycoefficient calculation where X_(A) and X_(B) are the mole fractions ofthe two competing guests in the original solution and Y_(A) and Y arethe mole fractions of the two competing guests in the host (Pivovar, A.M.; Holman, K. T.; Ward, M. D. Chem. Mater. 2011, 13, 3018-3031).

Selectivity coefficients for K_(MeCl:EtCl) and K_(MeCl:DME) weredetermined and averaged (with esds) over numerous trials where thecombined equivalents of gas bound in the cavitand were greater than0.10. These values can be seen in FIG. 8 (MeCl vs EtCl) and FIG. 9 (MeClvs DME). Experimental details as well as all raw data can be found inthe supplementary information. The diagonal black line seen in bothselectivity plots above denote no selectivity of host for anycompetitive guest (K_(A:B)=1). Curved lines for each set of competitionexperiments are shown as two standard deviations above and below theaverage selectivity coefficient calculated.

The preference of MeCl over EtCl for formula (Ib) is mainly due to guestsize and geometry. Both guests have a dipole moment, however the linearshape and smaller van der Waals volume of MeCl over EtCl show inclusionof the former to be more favorable. Furthermore, single crystalstructures of both inclusion complexes show very similar unit cellparameters for MeCl@formula (Ib) when compared to the native (empty)cavitand structure; there is a much larger deviation in unit cellparameters for EtCl@formula (Ib) as the cavitand must swell in order toaccommodate the much larger, bent guest.

Perhaps what is more intriguing is the much larger selectivity of MeClover DME. Since both guests have similar boiling points, typicalseparation methods by way of cryogenic distillation may prove to bedifficult. Also, chloromethane not only has the benefit of its linearshape, but its dipole makes it inherently more thermodynamically stablethan the 0.82(DME)@formula (Ib) inclusion complex, thus more likely tobe bound when in competition with the non-polar DME. This effect isalready seen as the DME does not fully occupy the cavitand in thesolid-state and though not as pronounced of an effect as that seen withEtCl@Me,H,SiMe₃, the unit cell parameters for the DME complex are moreexpanded than that of the MeCl clathrate.

TABLE 8 Summary data for precipitation and single crystal competitionexperiments. Ratio of gases determined by ¹H NMR of gas mixture. Ratioof gases after determined by ¹H NMR of cavitand inclusion complex. SCXRDratio was determined by the relative occupancies of both guests in thesolid-solution of cavitand using SHELXL refinement. Ratios are listedwith MeCl first. MeCl vs. EtCl MeCl vs. DME Precipitation Trial 1 Trial2 Trial 1 Trial 2 Ratio before (X) 1:24 1:30    1:21 1:14 Ratio after(Y) 1:1.17 1:1.49 1.63:1 1.68:1 K_(MeCl:EtCl or DME) 21 20 34 24 Yield49 mg 58 mg 32 mg 41 mg 69% 82% 45% 58% Single Crystal Ratio before (X)1:78    1:29 Ratio after (Y) 1:4.38 3.19:1 SCXRD ratio 1:3.23 2.52:1K_(MeCl:EtCl or DME) 18/24 93/73 (NMR/SCXRD)

Precipitation experiments were carried out to determine the approximateyields of the inclusion compounds as well as how the selectivity maychange when the experiment is performed over the course of a fewminutes. Nearly saturated solutions of formula (Ib) (71 mg in 1 mLCDCl₃) were taken and added to them were liquefied gas mixtures inexcess containing either more EtCl or DME over MeCl. Precipitationoccurred almost immediately and the equivalents of gases included aresummarized in Table 8.

The precipitation experiments show no real difference in MeClselectivity when competed against EtCl. This observation is notcongruent with MeCl vs. DME pairwise experiments. Fast precipitation ofthe cavitand without allowing for equilibrium to be establisheddiminishes the chloromethane selectivity since no time is allowed forthe more thermodynamic complex to form.

Single crystal growth of solid solutions containing both competingguests was achieved under dilute conditions (80 mg cavitand in 6 mLCDCl₃). Table 8 shows the equivalents of gas mixtures before thecompetition (by ¹H NMR) and the crystals after (¹H NMR and SCXRD). Inall cases, the ¹H NMR was in agreement with the equivalents of gas asdetermined by SHELXL refinement. Chloromethane selectivity over EtCl isnot improved when crystal growth conditions are employed. Using DME asthe competing guest, chloromethane inclusion is enhanced as more time isgiven for the more thermodynamically stable complex can be formed. Thethermal ellipsoid plots of the solid solutions can be seen in FIG. 11.All crystallographic information can be found in the supplementaryinformation.

Example 7: Synthesis of H,H,SiMe₂ Cavitand

Using a different synthetic route, the parent compound H,H,SiMe₂ wasalso synthesized and briefly studied for gas inclusion. This parentcompound lacks methyl groups on the rim of the cavitand, whichinherently gives it different/confinement properties of the guestsstudied. Indeed, gas inclusion complexes containing DME and MeCl wereisolated and studied by SCXRD. The guest free form of H,H,SiMe₂ wassublimed and its structure was determined to be the same as singlecrystals of the cavitand grown from ethyl acetate as the solvent is toolarge to complex into the cavity. Saturated ethyl acetate solutions ofH,H,SiMe₂ (12 mg per 1 mL) were exposed to the respective gases bybubbling through the solutions for 2-3 minutes. Vials containing thesolutions were then capped and heated to re-dissolve any precipitatethat may have formed and set aside.

Single crystals formed over the course of days to weeks and studied bySCXRD. Without the presence of any other competing guest, the cavitandshows remarkable inclusion selectivity of MeCl over DME. Inclusioncomplex 0.91 (MeCl)@H,H,SiMe₂ contains a mirror plane, a slightdeviation from the empty form (P2₁/n) however is almost fully occupiedby chloromethane. Conversely, 0.03(DME) 0.10 (H₂O)@H,H,SiMe₂ containsmostly water and as a result, shares the same space group as thesublimed, empty cavitand. The lack of DME inclusion is presumably due toits molecular geometry; this may also explain why we have been unable togrow single crystals of complexes containing EtCl in H,H,SiMe₂.

The cavity of the empty H,H,SiMe₂ is slightly larger than the formula(Ib) derivative using the same 1.4 Å probe radius and normalizing allC—H bonds to 1.08 Å. It would appear that it is thus better suited toaccommodate the larger DME guest, however the degree for which it mustexpand may be too significant to form the inclusion complex. Pairwiseexperiments of H,H,SiMe₂ with MeCl/EtCl or MeCl/DME run in the samemanner as described for formula (Ib) show no uptake of any gaseousguest.

Example 8: Synthesis of Empty Crystals of Formula (Ib) and HydrateCrystals of Formula Ib)

Calix[4]resorcinarene Me,H,OH was prepared by a literature method(Naumann, C.; Roman, E.; Peinador, C.; Ren, T.; Patrick, B. O.; Kaifer,A. E.; Sherman, J. C. Chem. Eur. J. 2001, 7, 1637-1645). Cavitandformula (Ib) was prepared as follows analogous to the procedure outlinedby Gibb et al. (Gibb, B. C.; Chapman, R. G.; Sherman, J. C. J. Org.Chem. 1996, 61, 1505-1509) for the synthesis of related cavitands andwas first reported by Lara-Ochoa et al. (Lara-Ochoa, F.; Garcia, M. M.;Teran, R.; Almaza, R. C.; Espinoza-Perez, G.; Chen, G.;Silaghi-Dumitrescu, I. Supramol. Chem. 2000, 11, 263).

x(H₂O)@Formula (Ib) (x(H₂O)@C₄₀H₄₈O₈Si₄)

Under N₂ atmosphere, calix[4]resorcinarene Me,H,OH (3.0 g, 5.5 mmol) wasdissolved in pyridine (180 mL), dichlorodimethylsilane (7.11 g, 6.64 mL,55.1 mmol) was rapidly added and the mixture was stirred for 48 hours atroom temperature. The solvent was then removed in vacuo and methanol wasadded (250 mL) to quench any unreacted Cl₂SiMe₂ and the solvent wasremoved by rotary evaporation. The material was triterated with methanoland the off-white solid was filtered and dried. The crude material wasthen dissolved in chloroform and run through a silica gel plug to givethe pure product as a partial hydrate in 68% yield (1.45 g, 1.88 mmol).M.P.=320-322° C. (onset of sublimation). ¹H NMR (400 MHz, CDCl₃): δ=7.16(s, 4H, ArH_(bottom)), 4.26 (d, ²J_(HH)=13.1 Hz, 4H, CH_(2(out))), 3.35(d, ²J_(HH)=13.1 Hz, 4H, CH_(2(in))), 1.93 (s, 12H, ArCH₃), 0.52 (s,12H, SiCH_(3(out))), −0.63 (s, 12H, SiCH_(3(in))) ppm. ¹³C NMR (100 MHz,CDCl₃): δ=148.63, 128.09, 127.03, 119.76, 32.25, 10.33, −3.03, −6.23ppm.

A single crystal of the partial cavitand hydrate 0.21(H₂O)@formula (Ib)was obtained by slow evaporation of formula (Ib) from wet chloroformsolution. A peak of 1.79 e⁻/Å³ was centered in the cavity and wasmodeled as a partial H₂O, refining to an occupancy of 0.21. Electrondensity SQUEEZE analysis estimated 1.75 e⁻ per cavitand cavity,corresponding to 0.18 eq. H₂O, this improved R₁ by 10% (0.0519 to0.0473.

Empty Formula (Ib)

This crystal was then subsequently dehydrated at 150° C. for 1 week in asingle-crystal-to-single-crystal fashion. A second data collection wasperformed on the crystal, which showed no peak (0.25 e⁻/Å³ well offsetfrom the center of the cavity). SQUEEZE analysis of this structure gave1.63 e⁻ per cavitand cavity. This demonstrates that the cavities areempty. A room temperature collection was obtained on another emptycrystal that was prepared from the partial hydrate in the same manner asdescribed above.

Crystal rehydration was carried out by placing the empty formula (Ib)crystal into a humidity chamber (100% RH) for 1 week at roomtemperature. Data collection of this crystal revealed a peak of 2.59e⁻/Å³, which refined to 0.28 occupancy of an oxygen atom (R₁ improvesfrom 0.0531 to 0.0447). SQUEEZE analysis estimates 3 electrons percavitand cavity, corresponding to an occupancy of 0.30 eq. of H₂O.

Example 9: Synthesis and Analysis of x(Guest)@Formula (Ib)

Half saturated solutions of empty formula (Ib) (generated by placingx(H₂O)@formula (Ib) in the oven at 150° C. for at least 2 days) inchloroform (solubility ˜80 mg/mL) were prepared and select gases werebubbled through the solutions until the chloroform evaporated and theresulting precipitated solids were dry. Nitrogen gas was then used topurge any remaining gas vapors from the vial before NMR measurements (˜3mins.). ¹H NMR spectra of the solids were obtained in CDCl₃ oracetone-δ₆ and the solid samples were again analyzed after 7 days ofstanding in ambient conditions. Multiple trials of these experimentswere carried out for select gases to ascertain errors for themeasurements. These spectra are denoted as day 0 or day 7 bubbling todryness experiments for a variety of gases and are shown in theSynthesis and Characterization section. The integrations in the spectrafor the guest and host protons are normalized to determine equivalentsof gas. In some instances, the signals of the guest overlap with signalsof the host; in this case, the integrations of the combined signals aresubtracted from the integration of a peak solely corresponding to thehost and subsequently normalized to determine equivalents.

Samples obtained from gas clathrates under pressurized conditions wereanalyzed the same way as described above. The day 0 and day 7 spectraare given for each sample in the Synthesis and Characterization section.In the instances where the included guest do not have any protons foranalysis, only a day 0 spectra was taken to check for proton-containingimpurities and to ensure that observed TGA mass losses are not due toimpurities.

xCH₃F@Formula (Ib)

Single crystals 0.80(CH₃F)@formula (Ib) (table S4) were obtained bybubbling fluoromethane into a saturated solution (approx. 0.1 M) offormula (Ib) in CHCl₃ until a precipitate formed, capping the glass vialand reheating to dissolve the remaining precipitate after which crystalsformed over days. SHELXL and SQUEEZE analysis estimated 0.77 and 0.83eq. of CH₃F per cavitand, respectively (average=0.80(4) eq./cavitand).Analysis of other crystals from batches prepared in the same manner gavethe same occupancies within error. Data collection of another crystalfrom the same batch shows a reduced fluoromethane occupancy of 0.43 eq.(after four months under ambient conditions) (table S4). In analogy tothat of the hydrate, this crystal was then heated at 150° C. for fourdays and its structure was re-determined by SCXRD; the occupancy wasfound to be 0.23 eq. CH₃F per cavitand. Subsequent heating of the samecrystal at 190° C. for 1 more week yielded the empty formula (Ib)crystal as shown by SCXRD analysis. These latter two collections havebeen omitted from the crystallographic data tables (below) due to theirredundancy with already reported structures, but the data is availableupon request.

xKr@Formula (Ib)

Single crystals of x(Kr)@formula (Ib) were grown under elevatedpressures by the following procedure. About 3±0.25 mL of krypton wascondensed in a cooled graduated cylinder and was poured into a cooledTeflon bomb (23 mL capacity) that was cooled in liquid nitrogen. A 1 mLsaturated solution of formula (Ib) in CHCl₃ with activated 3 Å molecularsieves in an uncapped GC-MS vial (1.5 mL capacity) was immediatelyplaced into the cooled Teflon bomb with the liquefied krypton. The bombwas quickly sealed in a metal jacket and set aside for 1-2 weeks. Thebomb was re-opened and the crystals of x(Kr)@formula (Ib) were filteredoff. A single crystal from the batch was studied by SCXRD and itscomposition was found to be 0.54(3)(Kr)@formula (Ib) (table S7)according to SHELXL refinement and SQUEEZE treatment of the data.Another single crystal from the same batch was found to have 0.50 eq. ofKr per cavitand (not reported). The original crystal was then heated at100° C. for two weeks and a subsequent SHELXL refinement showed a peakof 4.44 e⁻/Å³ that was centered in the cavity. The SQUEEZE subroutinegave 2.75 e⁻ per cavitand cavity corresponding to 0.07 eq. Kr. Theelectron density and peak position allows the conclusion that theelectrons correspond to residual krypton. Overall the SCXRD correlateswith the 0.07(Kr)@formula (Ib) inclusion complex.

TABLE S2 Crystallographic data for x(guest)@formula (Ib) CrystalParameters formula (Ib)^(a) formula (Ib)^(b) 0.21(H₂O)@formula (Ib)^(a)0.29(H₂O)@formula (Ib)^(a) Chemical formula C₄₀H₄₈O₈Si₄ C₄₀H₄₈O₈Si₄C₄₀H_(48.44)O_(8.21)Si₄ C₄₀H_(48.58)O_(8.29)Si₄ Formula weight, g/mol769.14 769.14 772.52 774.36 Growth Solvent CHCl₃ CHCl₃ CHCl₃ CHCl₃Crystal system Monoclinic Monoclinic Monoclinic Monoclinic Space groupC2/c C2/c C2/c C2/c Z 8 8 8 8 a, Å 23.8783(24) 23.9160(31) 23.8959(28)23.8634(18) b, Å 8.3377(9) 8.4243(11) 8.3362(10) 8.3296(6) c, Å42.1053(43) 42.4217(55) 42.0987(49) 42.0507(32) α, deg 90 90 90 90 β,deg 100.631(1) 100.521(2) 100.506(1) 100.508(1) γ, deg 90 90 90 90 V, Å³8238.9(15) 8403.2(19) 8245.5(17) 8218.3(11) ρ_(calc), g/cm³ 1.24 1.221.24 1.25 crystal dimensions, mm 1.6 × 1.5 × 0.96 0.82 × 0.63 × 0.36 1.6× 1.5 × 0.96 1.6 × 1.5 × 0.96 T, K 100(2) 296(2) 100(2) 100(2) 2Θ maxfor refinement, deg 56.0 56.0 56.0 56.0 total reflections 34790 3187035219 31061 independent reflections 9663 9900 9653 9631 no. of observeddata 7342 5314 6795 7799 no. of parameters 477 477 490 490 R_(int)0.0455 0.0741 0.1154 0.0365 μ, mm⁻¹ 0.193 0.189 0.194 0.195 R₁(F),wR₂(F²), (I > 2σ(I)) 0.0473, 0.1309 0.0447, 0.1019 0.0473, 0.11660.0447, 0.1146 Goodness-of-fit on F² 1.066 0.861 0.972 0.85 CCDCDepository Number 895245 895246 895247 895248 ^(a)Same crystal ^(b)Note:room temp. data.

TABLE S3 Crystallographic data for x(guest)@formula (Ib) CrystalParameters CH₃I@formula (Ib) CH₃Br@formula (Ib) CH₃Cl@formula (Ib)CH₃Cl@formula (Ib) Chemical formula C₄₁H₅₃O₈Si₄I C₄₁H₅₃O₈Si₄BrC₄₁H₅₁O₈Si₄Cl C₄₁H₅₁O₈Si₄Cl Formula weight, g/mol 911.08 864.09 819.63819.63 Growth Solvent CHCl₃ CHCl₃ CHCl₃ EtOAc Crystal system MonoclinicMonoclinic Monoclinic Monoclinic Space group C2/c C2/c C2/c C2/c Z 8 8 88 a, Å 23.7418(15) 23.7815(29) 23.8190(24) 23.7820(26) b, Å 8.3761(5)8.3577(10) 8.3375(9) 8.3354(9) c, Å 42.6673(28) 42.3173(52) 42.2158(43)42.2278(46) α, deg 90 90 90 90 β, deg 99.403(1) 98.998(2) 99.032(1)98.903(1) γ, deg 90 90 90 90 V, Å³ 8371.0(9) 8307.4(17) 8279.7(15)8270.1(16) ρ_(calc), g/cm³ 1.47 1.38 1.32 1.32 crystal dimensions, mm0.60 × 0.42 × 0.27 0.23 × 0.17 × 0.13 1.0 × 0.70 × 0.70 0.53 × 0.20 ×0.20 T, K 100(2) 100(2) 100(2) 100(2) 2Θ max for refinement, 56.0 56.056.0 56.0 deg total reflections 31937 94190 35918 31511 independentreflections 9883 10023 9807 9757 no. of observed data 7621 8773 76096733 no. of parameters 501 501 501 501 R_(int) 0.0464 0.0538 0.05170.0658 μ, mm⁻¹ 0.93 1.156 0.259 0.259 R₁(F), wR₂(F²), (I > 2σ(I))0.0515, 0.1231 0.0537, 0.1286 0.0521, 0.1351 0.0481, 0.1045Goodness-of-fit on F² 1.176 1.351 1.06 1.05 CCDC Depository 895249895250 895251 895252 Number

TABLE S4 Crystallographic data for x(guest)@formula (Ib) CrystalParameters 0.80(CH₃F)@formula (Ib) 0.43(CH₃F)@formula (Ib)^(a)EtCl@formula (Ib) 0.74(BrCH₂Cl)@formula (Ib) Chemical formulaC_(40.8)H_(50.4)O₈Si₄F_(0.80) C_(40.43)H_(49.29)O₈Si₄F_(0.43)C₄₂H₅₅O₈Si₄Cl C_(40.74)H_(59.48)O₈Si₄Cl_(0.74)Br_(0.74) Formula weight,g/mol 796.37 783.78 829.80 864.90 Growth Solvent CHCl₃ CHCl₃ CHCl₃BrCH₂Cl Crystal system Monoclinic Monoclinic Monoclinic Monoclinic Spacegroup C2/c C2/c C2/c C2/c Z 8 8 8 8 a, Å 23.8281(25) 23.8507(27)23.5981(20) 23.7650(20) b, Å 8.3065(9) 8.3122(9) 8.4762(7) 8.4219(7) c,Å 42.1464(44) 42.1008(47) 42.8436(35) 42.7905(36) α, deg 90 90 90 90 β,deg 99.653(1) 100.069(1) 99.750(1) 101.108(1) γ, deg 90 90 90 90 V, Å³8223.8(15) 8218.0(16) 8445.9(12) 8403.9(12) ρ_(calc), g/cm³ 1.29 1.271.31 1.37 crystal dimensions, mm 1.49 × 0.38 × 0.26 0.86 × 0.67 × 0.290.76 × 0.33 × 0.32 0.82 × 0.43 × 0.21 T, K 100(2) 100(2) 100(2) 100(2)2Θ max for refinement, deg 56.0 56.0 56.0 56.0 total reflections 3104931231 36561 35425 independent reflections 9667 9656 10002 9891 no. ofobserved data 7338 6756 8408 7435 no. of parameters 501 501 510 541R_(int) 0.0506 0.0567 0.0311 0.0427 μ, mm⁻¹ 0.199 0.196 0.251 0.943R₁(F), wR₂(F²), (I > 2σ(I)) 0.0540, 0.1103 0.0503, 0.1148 0.0411, 0.09530.0555, 0.1208 Goodness-of-fit on F² 1.048 1.064 1.019 1.044 CCDCDepository Number 895253 895254 895255 895256 ^(a)Different crystal,from the same batch as 0.80(CH₃F)@formula (Ib) but after 4 months atambient conditions.

TABLE S5 Crystallographic data for x(guest)@formula (Ib)0.85(CH₂Cl₂)@formula 0.82(CH₃OCH₃)@formula 0.83(CH₃SH)@formula0.06(I₂)@formula Crystal Parameters (Ib) (Ib) (Ib) (Ib) Chemical formulaC_(40.85)H_(49.7)O₈Si₄Cl_(1.7) C_(41.64)H_(52.92)O_(8.82)Si₄C_(40.83)H_(51.32)O₈Si₄S_(0.83) C₄₀H₄₈O₈Si₄I_(0.12) Formula weight,g/mol 841.35 806.94 809.09 784.37 Growth Solvent CH₂Cl₂ CHCl₃ CHCl₃CHCl₃ Crystal system Monoclinic Monoclinic Monoclinic Monoclinic Spacegroup C2/c C2/c C2/c C2/c Z 8 8 8 8 a, Å 23.8439(22) 23.8115(22)23.8489(14) 23.8600(12) b, Å 8.3749(8) 8.3707(8) 8.3186(5) 8.3389(4) c,Å 42.7877(39) 42.6458(40) 42.2892(26) 42.1352(22) α, deg 90 90 90 90 β,deg 101.337(1) 100.829(1) 99.377(1) 100.525(1) γ, deg 90 90 90 90 V, Å³8377.6(13) 8348.7(14) 8277.6(9) 8242.4(7) ρ_(calc), g/cm³ 1.33 1.28 1.301.26 crystal dimensions, 0.36 × 0.26 × 0.26 0.87 × 0.72 × 0.11 0.47 ×0.15 × 0.11 0.47 × 0.38 × 0.07 mm T, K 100(2) 100(2) 100(2) 100(2) 2Θmax for 56.0 56.0 56.0 56.0 refinement, deg total reflections 3648031519 109616 35677 independent reflections 9939 9787 9981 9737 no. ofobserved data 7379 7632 9164 7451 no. of parameters 508 511 501 508R_(int) 0.0467 0.0459 0.0411 0.042 μ, mm⁻¹ 0.301 0.195 0.236 0.283R₁(F), wR₂(F²), (I > 0.0461, 0.1059 0.0522, 0.1195 0.0501, 0.11820.0556, 0.1270 2σ(I)) Goodness-of-fit on F² 1.051 1.031 1.131 1.056 CCDCDepository No. 895257 895258 895259 895271

TABLE S6 Crystallographic data for x(guest)@formula (Ib) CrystalParameters 0.72(C₂H₆)@formula (Ib)^(a) 0.75(C₂H₆)@formula (Ib)^(a)0.77(Xe)@formula (Ib) 0.79(Xe)@formula (Ib)^(b) Chemical formulaC_(41.44)H_(52.32)O₈Si₄ C_(41.50)H_(52.50)O₈Si₄ C₄₀H₄₈O₈Si₄Xe_(0.77)C₄₀H₄₈O₈Si₄Xe_(0.79) Formula weight, g/mol 790.79 791.71 870.24 872.88Growth Solvent CHCl₃ CHCl₃ CHCl₃ CHCl₃ Crystal system MonoclinicMonoclinic Monoclinic Monoclinic Space group C2/c C2/c C2/c C2/c Z 8 8 88 a, Å 23.7918(15) 23.8033(13) 23.7847(20) 23.7967(66) b, Å 8.3456(5)8.3453(4) 8.3252(7) 8.3333(23) c, Å 42.2677(26) 42.2733(23) 42.2368(35)42.2748(117) α, deg 90 90 90 90 β, deg 99.785(1) 99.789(1) 99.359(1)99.380(4) γ, deg 90 90 90 90 V, Å³ 8270.5(10) 8275.1(8) 8252.1(12)8271(4) ρ_(calc), g/cm³ 1.27 1.27 1.40 1.40 crystal dimensions, mm 0.60× 0.36 × 0.35 0.60 × 0.36 × 0.35 0.40 × 0.20 × 0.12 0.45 × 0.11 × 0.10T, K 100(2) 100(2) 100(2) 100(2) 2Θ max for refinement, deg 56.0 56.056.0 56.0 total reflections 31373 35753 30957 34741 independentreflections 9719 9738 9679 9737 no. of observed data 7880 8704 7851 6909no. of parameters 501 503 490 491 R_(int) 0.0383 0.0248 0.0458 0.069 μ,mm⁻¹ 0.194 0.194 0.815 0.83 R₁(F), wR₂(F²), (I > 2σ(I)) 0.0500, 0.11010.0515, 0.1155 0.0559, 0.1061 0.0564, 0.1238 Goodness-of-fit on F² 1.0621.140 1.161 1.085 CCDC Depository Number 895260 895261 895262 895263^(a)Same crystal, the 2^(nd) data collection occurring after 10 days atambient conditions. ^(b)Different crystal from the same batch as0.77(Xe)@formula (Ib) but after 129 days at ambient conditions.

TABLE S7 Crystallographic data for x(guest)@formula (Ib)0.41(C₂H₄)@formula 0.54(Kr)@formula 0.07(Kr)@formula Crystal Parameters(Ib)^(a) 0.43(C₂H₄),0.22(H₂O)@formula (Ib)^(a) (Ib) (Ib)^(b) Chemicalformula C_(40.82)H_(49.64)O₈Si₄ C_(40.86)H_(50.16)O_(8.22)Si₄C₄₀H₄₈O₈Si₄Kr_(0.54) C₄₀H₄₈O₈Si₄Kr_(0.07) Formula weight, g/mol 780.65785.19 814.4 775.03 Growth Solvent CHCl₃ CHCl₃ CHCl₃ CHCl₃ Crystalsystem Monoclinic Monoclinic Monoclinic Monoclinic Space group C2/c C2/cC2/c C2/c Z 8 8 8 8 a, Å 23.8487(12) 23.8543(13) 23.8156(27) 23.8513(17)b, Å 8.3237(4) 8.3318(4) 8.3314(10) 8.3338(6) c, Å 42.0407(21)42.0514(22) 42.0998(48) 42.0596(30) α, deg 90 90 90 90 β, deg 99.880(1)99.836(1) 99.948(1) 100.528(1) γ, deg 90 90 90 90 V, Å³ 8226.6(7)8234.8(7) 8227.7(17) 8219.5(10) ρ_(calc), g/cm³ 1.26 1.27 1.32 1.25crystal dimensions, mm 0.58 × 0.31 × 0.19 0.58 × 0.31 × 0.19 0.50 × 0.34× 0.22 0.49 × 0.14 × 0.11 T, K 100(2) 100(2) 100(2) 100(2) 2Θ max forrefinement, 56.0 56.0 56.0 56.0 deg total reflections 34703 31321 3487734617 independent reflections 9663 9729 9740 9686 no. of observed data7762 7763 6170 6518 no. of parameters 499 504 491 491 R_(int) 0.03320.195 0.771 0.0691 μ, mm⁻¹ 0.195 0.0363 0.0814 0.269 R₁(F), wR₂(F²),(I > 0.0428, 0.1038 0.0441, 0.1065 0.0411, 0.0877 0.0540, 0.1118 2σ(I))Goodness-of-fit on F² 1.039 1.041 0.812 1.026 CCDC Depository No. 895264895265 895266 895267

TABLE S8 Crystallographic data for x(guest)@formula (Ib) CrystalParameters 0.29(Ar)@formula (Ib)^(a) 0.25(Ar)@formula (Ib)^(a)0.46(CO₂)@formula (Ib)^(b) 0.36(CO₂)@formula (Ib)^(b) Chemical formulaC₄₀H₄₈O₈Si₄Ar_(0.29) C₄₀H₄₈O₈Si₄Ar_(0.25) C_(40.46)H₄₈O_(8.92)Si₄C_(40.36)H₄₈O_(8.72)Si₄ Formula weight, g/mol 780.73 779.15 789.4 789.4Growth Solvent CHCl₃ CHCl₃ CHCl₃ CHCl₃ Crystal system MonoclinicMonoclinic Monoclinic Monoclinic Space group C2/c C2/c C2/c C2/c Z 8 8 88 a, Å 23.8429(12) 23.8592(17) 23.9014(24) 23.9014(24) b, Å 8.3337(4)8.3364(6) 8.3164(8) 8.3164(8) c, Å 42.0738(22) 42.0622(31) 41.9864(43)41.9864(43) α, deg 90 90 90 90 β, deg 100.309(1) 100.351(1) 100.205(1)100.205(1) γ, deg 90 90 90 90 V, Å³ 8225.1(7) 8230.0(10) 8213.8(14)8213.8(14) ρ_(calc), g/cm³ 1.26 1.26 1.28 1.28 crystal dimensions, mm0.56 × 0.24 × 0.17 0.56 × 0.24 × 0.17 0.64 × 0.51 × 0.20 0.64 × 0.51 ×0.20 T, K 100(2) 100(2) 100(2) 100(2) 2Θ max for refinement, deg 56.056.0 56.0 56.0 total reflections 35014 31362 34738 34738 independentreflections 9758 9724 9668 9668 no. of observed data 7865 6753 6969 6969no. of parameters 490 490 509 509 R_(int) 0.0342 0.0633 0.0519 0.0519 μ,mm⁻¹ 0.218 0.214 0.197 0.197 R₁(F), wR₂(F²), (I > 2σ(I)) 0.0468, 0.11150.0522, 0.1062 0.0475, 0.1145 0.0475, 0.1145 Goodness-of-fit on F² 1.0481.032 1.114 1.114 CCDC Depository Number 895268 895269 895270 895460

TABLE S9 Crystallographic data for x(guest)@formula (Ib) CrystalParameters 0.26(CH₄)@formula (Ib)^(a) CH₃CN@formula (Ib) NO₂CH₃@formula(Ib) 0.67(CH₃OH)@formula (Ib) Chemical formula C_(40.26)H_(49.04)O₈Si₄C₄₂H₅₁O₈Si₄N C₄₁H₅₁O₁₀Si₄N C_(40.67)H_(50.68)O_(8.67)Si₄ Formula weight,g/mol 773.31 810.2 830.19 790.61 Growth Solvent CHCl₃ CH₃CN NO₂CH₃CHCl₃/MeOH Crystal system Monoclinic Monoclinic Monoclinic MonoclinicSpace group C2/c C2/c C2/c C2/c Z 8 8 8 8 a, Å 23.9345(127) 23.8211(29)23.9220(31) 23.9064(22) b, Å 8.3621(45) 8.3280(12) 8.2830(11) 8.3015(8)c, Å 42.1566(223) 42.0611(62) 42.4669(54) 42.1497(39) α, deg 90 90 90 90β, deg 100.501(6) 98.894(2) 100.387(1) 100.301(1) γ, deg 90 90 90 90 V,Å³ 8296(8) 8244(2) 8276.7(19) 8230.2(13) ρ_(calc), g/cm³ 1.24 1.31 1.331.28 crystal dimensions, mm 0.63 × 0.30 × 0.20 0.41 × 0.13 × 0.13 0.45 ×0.42 × 0.41 0.45 × 0.42 × 0.41 T, K 100(2) 100(2) 100(2) 100(2) 2Θ maxfor refinement, deg 56.0 56.0 56.0 56.0 total reflections 34542 3511835023 34888 independent reflections 9684 9621 9736 9732 no. of observeddata 7111 6337 8235 6603 no. of parameters 486 510 519 502 R_(int)0.0516 0.0728 0.0298 0.0636 μ, mm⁻¹ 0.192 0.197 0.202 0.196 R₁(F),wR₂(F²), (I > 2σ(I)) 0.0478, 0.1109 0.0554, 0.1226 0.0412, 0.10380.0522, 0.1151 Goodness-of-fit on F² 1.042 1.044 1.045 1.079 CCDCDepository Number 895459 895272 895273 895274

Example 10: Gas Clathrate Synthetic Growth Method

Ambient conditions: the gas of interest was bubbled into a saturatedCHCl₃ solution of formula (Ib) (1-2 mL) in a borosilicate glass vialuntil a precipitate started to form. The vial was then capped andreheated to redissolve the precipitate and set aside until crystalsformed, usually on the order of hours/days.

Elevated pressures: CAUTION! This method uses liquefied gases underpressures in a closed system. A proper amount of liquid gas wasdetermined by using the van der Waals equation of state so as to notexceed ˜80 atm (Teflon bombs rated up to ˜120 atm) in about 20 mL ofempty volume. From this calculation, an estimated maximum pressure canbe determined (P_(est)), since solubility of the gas in chloroform isnot accounted for and would thus decrease the total pressure in thevessel. The teflon bomb was cooled in liquid nitrogen and then placedinto a metal jacket (cooling of the bomb was done with the teflon cap onso as to minimize condensation of water inside). Added to it was thepredetermined amount of liquefied gas (or solid in the case of CO2) anda 1 mL saturated solution of formula (Ib) in CHCl₃ with activated 3 Åmolecular sieves in an uncapped GC-MS vial (1.5 mL capacity) and thebomb was quickly sealed in a metal jacket, allowed to warm to roomtemperature and set aside for 1-2 weeks. The bomb was re-opened and thecrystals of x(gas)@formula (Ib) were filtered off.

0.26(CH₄)@Formula (Ib)

Single crystals of a methane clathrate were prepared by the elevatedpressure method defined above using 3 mL of CH₄ (P_(est)≤70 atm). Thisgave single crystals that were analyzed by SCXRD, TGA and ¹H NMRspectroscopy. Refinement of the SCXRD data revealed a peak of 1.3 e⁻/Å³confined in the cavity. The peak was modeled as a carbon atom with arefined occupancy of 0.26 (Table S9). SQUEEZE analysis of this structuregave 2.13 e⁻ per cavitand cavity (0.21 eq.). We note that by SCXRD, thepurported partial occupancy methane molecule is indistinguishable from apartially occupied water molecule and the structure could as easily berefined as a partial hydrate. ¹H NMR analysis of the crystals, however,shows at least 0.04 eq. of methane per cavitand. The differences inoccupancies between SCXRD and ¹H NMR may be due to escaping gas upondissolution of the cavitand inclusion complex. TGA data shows 0.5 weightloss percent to 240° C., however it is not conclusive that methane isthe guest in the cavity

x(Kr)@Formula (Ib)

Single crystals of a krypton clathrate were prepared by the elevatedpressure method defined above using 3 mL of Kr (P_(est)≤70 atm). Thisgave single crystals of 0.54(Ar)@formula (Ib) that were analyzed bySCXRD upon isolation (Table S7). Another crystal that was analyzed fromthe same batch contained 0.50 eq. of krypton per cavitand (notreported). This single crystal was then heated at 100° C. for two weeksand was shown to possess only 0.07 eq. of krypton by SCXRD (Table S7).TGA studies show 14% guest loss over a 7 day span (0.96 eq. to 0.82 eq.Kr). The sample at day 7 was analyzed by TGA-MS and showed clearly therelease of Kr (m/Z=84 amu) concomitant with mass loss. ¹H NMR at day 0shows no impurities that would be responsible for the mass loss.

x(Xe)@Formula (Ib)

Single crystals of a xenon clathrate were prepared by the elevatedpressure method defined above using 3 mL of Xe (P_(est)≤50 atm). Thisgave single crystals of 0.77(Xe)@formula (Ib) that were analyzed bySCXRD upon isolation (Table S6). Another crystal that was analyzed fromthe same batch after 129 days and gave the same occupancy within error(0.79 eq. Xe/cavitand) (Table S6). TGA studies on the bulkmicrocrystalline material shows 19% guest loss over a 7 day span (0.93eq. to 0.73 eq. Xe) The sample at day 7 was analyzed by TGA-MS andshowed clearly the release of Xe (m/z=131 amu) concomitant with massloss. ¹H NMR at day 0 shows no impurities that would be responsible forthe mass loss.

x(C₂H₄)@Formula (Ib)

Ethylene gas was bubbled into a saturated solution of formula (Ib) inCHCl₃ (1 mL) until dryness. The powder was placed in a stream ofnitrogen for 1 min. and analyzed by ¹H NMR after nitrogen purge and 7days later. Single crystals of an ethylene clathrate were prepared bythe elevated pressure method defined above using 3 mL of C₂H₄(P_(est)≤45atm). This gave single crystals of 0.41(C₂H₄)@formula (Ib) that wereanalyzed by SCXRD upon isolation (Table S7). The same crystal wasanalyzed 7 days later by SCXRD and was found to be0.43(C₂H₄).0.22(H₂O)@formula (Ib) (Table S7). Inclusion of water in theday 7 crystal structure can be attributed to the single crystal standingin ambient conditions between day 0 and day 7 SCXRD collections and theuptake of water. TGA studies show corresponding mass loss (0.28 eq.C₂H₄) and ¹H NMR at day 0 and 7 shows 0.06 and 0.04 eq. of ethylene,respectively. The differences in occupancies between SCXRD and ¹H NMRmay be due to escaping gas upon dissolution of the cavitand inclusioncomplex.

x(C₂H₆)@Formula (Ib)

Ethane gas was bubbled into a saturated solution of formula (Ib) inCHCl₃ (1 mL) until dryness. The powder was placed in a stream ofnitrogen for 1 min. and analyzed by ¹H NMR after nitrogen purge and 7days later. Single crystals of an ethane clathrate were prepared by theelevated pressure method defined above using 4 mL of C₂H₆(P_(est)≤40atm). This gave single crystals of 0.72(C₂H)@formula (Ib) that wereanalyzed by SCXRD upon isolation. The same crystal studied 10 days laterby SCXRD showed 0.75 eq. C₂H₆/cavitand (Table S6). TGA studiesconsistently showed weight loss % values that were 2-3 times theexpected mass loss. We conjecture that a small amount of the cavitandco-sublimes simultaneously with the loss of ethane. Despite theseinconsistencies, tandem TGA-MS clearly shows the release of ethane(m/z=32 amu) to be concomitant with the mass loss. Also, by placing thematerial in a sealed DSC pan (with hole for gas escape) and using thesame TGA protocol, the correct weight loss % was determined. ¹H NMR atday 0 and 16 of batch crystals shows 0.38 and 0.35 eq. of ethane,respectively. The differences in occupancies between SCXRD and ¹H NMRmay be due to escaping gas upon dissolution of the cavitand inclusioncomplex.

x(C₂H₂)@Formula (Ib)

Acetylene gas (generated by the addition of water to calcium carbide)was bubbled into a saturated solution of formula (Ib) in CHCl₃ (1 mL)until dryness. The powder was placed in a stream of nitrogen for 1minute and analyzed by ¹H NMR after treatment with nitrogen and 7 dayslater.

x(C_(x)F)@Formula (Ib)

Fluoromethane was also bubbled into a saturated solution of formula (Ib)in CHCl₃ (1 mL) until dryness. The powder was placed in a stream ofnitrogen for 1 min. and analyzed by ¹H NMR after nitrogen purge and 7days later. These show occupancies of 0.56 and 0.28 eq. offluoromethane, respectively. Fluoromethane clathrates were grown underthe ambient conditions method outlined above. Single crystals thatformed over the course of 1-2 weeks to were analyzed by SCXRD andrefined to 0.80(CH₃F)@formula (Ib). A single crystal studied by SCXRDfrom the same batch after 4 months later gave an occupancy of 0.43 eq.CH₃F/cavitand (Table S4). TGA studies show corresponding mass loss atday 0. The differences in occupancies between SCXRD and ¹H NMR may bedue to escaping gas upon dissolution of the cavitand inclusion complex.

x(CO₂)@Formula (Ib)

Single crystals of a carbon dioxide clathrate were prepared by theelevated pressure method defined above using 5 g of CO₂ (P_(est)≤60atm). This gave single crystals of 0.46(CO₂)@formula (Ib) that wereanalyzed by SCXRD upon isolation. The same crystal 7 days later wasfound to contain 0.36 eq. of CO₂ (Table S8). TGA studies show 9% guestloss over a 7 day span (0.40 eq. to 0.35 eq. CO₂/cavitand). TandemTGA-MS measurements were made on a 2^(nd) batch of x(CO₂)@formula (Ib)that clearly shows the release of CO₂ (m/z=44 amu) to be concomitantwith the mass loss

CH₃Cl@Formula (Ib)

Chloromethane was bubbled into a saturated solution of formula (Ib) inCHCl₃ (1 mL) until dryness. The powder was placed in a stream ofnitrogen for 1 min. and analyzed by ¹H NMR after nitrogen purge and 7days later. These show occupancies of 1.0 and 0.84 eq. of chloromethane,respectively. Chloromethane clathrates were grown under the ambientconditions method outlined above. Single crystals that formed over thecourse of 1-2 weeks were analyzed by SCXRD were refined to CH₃Cl@formula(Ib) (Table S3). Single crystals of chloromethane under the ambientconditions method were also grown out of ethyl acetate and were shown tobe also be fully occupied by chloromethane (Table S3). TGA studies showa mass loss corresponding to 1.04 eq. CH₃Cl (grown from chloroformsolution).

0.82(CH₃OCH₃)@Formula (Ib)

Dimethylether (DME) was bubbled into a saturated solution of formula(Ib) in CHCl₃ (1 mL) until dryness. The powder was placed in a stream ofnitrogen for 1 min. and later by ¹H NMR after nitrogen purge (0.36 eq.)and after 7 days (0.34 eq.). Single crystals of a DME clathrate wereprepared by the elevated pressure method defined above using 3 mL ofCH₃OCH₃ (P_(est)≤6 atm). This gave single crystals of0.82(CH₃OCH₃)@formula (Ib) that were analyzed by SCXRD upon isolation(Table S5). Different occupancies between SCXRD and ¹H NMR may be due toescaping gas upon dissolution of the complex.

CH₃CCH@Formula (Ib).2CHCl₃

Propyne was bubbled into a saturated solution of formula (Ib) in CHCl₃(1 mL) until dryness. The powder was placed in a stream of nitrogen for1 min. and later by ¹H NMR after nitrogen purge and after 7 days.Propyne clathrates were grown under the ambient conditions methodoutlined above. Single crystals of the complex were studied by SCXRD anddetermined to be CH₃CCH@formula (Ib) 2CHCl₃ (Table S10). TGA data couldnot be obtained due to the rapid loss of propyne and chloroform whilegrinding during sample preparation. ¹H NMR analysis at day 0 and day 7shows 1 eq. of propyne per cavitand initially, followed by no trace ofthe gas, respectively.

CH₃Br@Formula (Ib)

Bromomethane clathrates were grown under the ambient conditions methodoutlined above. Single crystals that formed over the course of 1-2 weekswere analyzed by SCXRD and refined to CH₃Br@formula (Ib) (Table S3). TGAstudies show a mass loss corresponding to 1.08 eq. CH₃Br per cavitand.The percentage was taken at the lowest rate of guest loss beforesublimation.

0.83(CH₃SH)@Formula (Ib)

Methanethiol clathrates were grown under the ambient conditions methodoutlined above. Single crystals that formed over the course of 1-2 weekswere analyzed by SCXRD and refined to 0.83(CH₃SH)@formula (Ib) (TableS5). TGA data of inclusion compound was not meaningful.

EtCl@Formula (Ib)

A saturated solution of formula (Ib) in CHCl₃ (1 mL) was placed in aglass screw cap vial with 5 mL of EtCl_((l)) and sealed 2 days (P˜2atm). Single crystals formed within 1 hour to yield EtCl@formula (Ib)that were analyzed by SCXRD (Table S4). ¹H NMR shows 0.98 eq. of EtClper cavitand.

0.85(CH₂Cl₂)@Formula (Ib)

Formula (Ib) was dissolved in dichloromethane and slow evaporation ofthe solvent yielded single crystals of (0.85)CH₂Cl₂@formula (Ib) thatwere analyzed by SCXRD (Table S5) (ORTEP is shown below). TGA data showsa mass loss corresponding to 0.97 eq. CH₂Cl₂ per cavitand. ¹H NMR shows0.84 eq. of CH₂Cl₂ per cavitand.

CH₃I@Formula (Ib)

Formula (Ib) was dissolved in iodomethane and slow evaporation of thesolvent yielded single crystals of CH₃I@formula (Ib) that were analyzedby SCXRD (Table S3). TGA data shows 1.05 eq. of CH₃I per cavitand.

0.67(CH₃OH)@Formula (Ib)

A saturated solution of formula (Ib) in CHCl₃ (1 mL) was placed in aglass screw cap vial with 3 mL of MeOH and heated to re-dissolve anyprecipitate. Single crystals of 0.67(CH₃OH)@formula (Ib) grew within 1-2days and were analyzed by SCXRD (Table S9) (ORTEP shown below). TGA datashows a mass loss corresponding to 0.9 eq. of CH₃OH per cavitand. ¹H NMRshows 0.56 eq. of CH₃OH per cavitand.

0.74(BrCH₂Cl)@Formula (Ib)

formula (Ib) was dissolved in bromochloromethane and slow evaporation ofthe solvent yielded single crystals of 0.74(BrCH₂Cl)@formula (Ib) thatwere analyzed by SCXRD (Table S4) (ORTEP shown below). TGA data shows amass loss corresponding to 0.63 eq. of BrCH₂Cl per cavitand. ¹H NMRshows 0.62 eq. of BrCH₂Cl per cavitand.

0.13(EtOH)@Formula (Ib)

A saturated solution of formula (Ib) in CHCl₃ (1 mL) was placed in aglass screw cap vial with 3 mL of EtOH and heated to re-dissolve anyprecipitate. Single crystals of 0.13(EtOH)@formula (Ib) grew within 1-2days and analyzed by SCXRD (Table S10) (ORTEP shown below). TGA datashows a mass loss corresponding to release of EtOH and sublimationsimultaneously. ¹H NMR shows 0.11 eq. of EtOH per cavitand.

CH₃CN@Formula (Ib)

Formula (Ib) was dissolved in acetonitrile and slow evaporation of thesolvent yielded single crystals of 0.97(CH₃CN)@formula (Ib) that wereanalyzed by SCXRD (Table S9) (ORTEP shown below). TGA data shows a massloss corresponding to release of CH₃CN and sublimation simultaneously.¹H NMR shows 0.96 eq. of CH₃CN per cavitand.

0.09(CH₂Br₂)@Formula (b)

Formula (Ib) was dissolved in dibromomethane and slow evaporation of thesolvent yielded single crystals of 0.09(CH₂Br₂)@formula (Ib) that wereanalyzed by SCXRD. Crystal structure shows residual electron density inthe cavitand cavity that was not modeled. The occupancy ofdibromomethane was ascertained by SQUEEZE calculation. TGA data shows amass loss corresponding to 0.10 eq. of CH₂Br₂ per cavitand. ¹H NMR shows0.08 eq. of CH₂Br₂ per cavitand.

NO₂CH₃@Formula (Ib)

Formula (Ib) was dissolved in nitromethane and slow evaporation of thesolvent yielded single crystals of NO₂CH₃@formula (Ib) that wereanalyzed by SCXRD (Table S9) (ORTEP shown below). TGA data shows a massloss corresponding to release of NO₂CH₃ and sublimation simultaneously.¹H NMR shows 0.87 eq. of NO₂CH₃ per cavitand.

x(H₂O)@Formula (Ib)

Single crystals of x(H₂O)@formula (Ib) were made from bulk formula (Ib)from slow evaporation of ethyl acetate (x), acetone (x=0.38), THF(x=0.24) and chloroform (x=0.21) solutions of formula (Ib). The hydrategrown from chloroform solution is reported in Table S2. This crystal wasplaced in an oven at 150° C. for at least 2 days and was subsequentlyplaced in a humidity chamber at room temperature for 1 week to give the0.28 eq. hydrate (Table S2). The TGA data shows typical mass loss forx(H₂O)@formula (Ib).

0.06(I₂)@Formula (Ib)

Approximately 10 mg of I₂ was added to a saturated solution of formula(Ib) in CHCl₃ (1 mL) and slow evaporation of the solvent yielded singlecrystals of 0.06(I₂)@formula (Ib) that were analyzed by SCXRD (Table S5)(ORTEP shown below). TGA data shows a mass loss corresponding to 0.06eq. of I₂ per cavitand.

Example 11: Separations Experiments with EtCl, MeCl and DME UsingCrystalline Compositions of Formula (Ib)

Bulk x(HO)@formula (Ib) was prepared. The powder can be activated at150° C. over two days before use in separations experiments. Activated,empty formula (Ib) (approximately 50 mg) was placed in Teflon bomb alongwith liquefied MeCl and EtCl or MeCl and DME and sealed for 2 days. Thegas present in the smallest amount (usually MeCl) was always in muchhigher excess than cavitand (approximately 10-20×).

The ¹H NMR of the gas mixture was taken before adding to the Teflon bombto determine the mole fractions of the gases (X_(MeCl) andX_(EtCl or DME)). After 2 days, the bombs were placed into liquidnitrogen to re-condense the gases inside, opened, and the suspension wasfiltered off (cooling method). Some of the bombs were opened withoutcooling and the liquid gases let evaporate to determine if there is asignificant difference in selectivity numbers (evaporation method).Other pairwise experiments involved pouring the liquefied gas mixtureinto a saturated solution of cavitand in chloroform (˜0.1 M), whichinduced precipitation within seconds (precipitation method). These werefiltered off after 1 hour and analyzed further.

Preparation of solid solutions involved pouring the liquefied gasmixtures into more dilute solutions of cavitand in chloroform (˜17 mM)and waiting for single crystals to form to be analyzed by NMR and SCXRD(solid-solution method). The ¹H NMR of the solids were then taken todetermine the mole fraction of gases that were bound by formula (Ib)(Y_(MeCl) and Y_(EtCl or DME)). Selectivity coefficients were thendetermined for experiments in which the total amount of bound gases waslarger than 0.10 eq. per cavitand. These values were then averaged andthe standard deviation determined to give the overall selectivitycoefficient over several trials.

TABLE S10 Crystallographic Data x(CH₃Cl)•y(Guest)@formula (Ib). CrystalParameters 0.22(CH₃Cl)•0.71(EtCl)@formula (Ib)0.63(CH₃Cl)•0.25(DME)@formula (Ib) Chemical formulaC_(41.61)H_(52.21)O₈Si₄Cl_(0.93) C_(41.13)H_(51.39)O_(8.25)Si₄Cl_(0.63)Formula weight, g/mol 826.07 812.48 Solvent CHCl₃/CH₃Cl/EtClCHCl₃/CH₃Cl/DME Crystal system Monoclinic Monoclinic Space group C2/cC2/c Z 8 8 a, Å 23.6217(52) 23.7861(29) b, Å 8.4439(19) 8.3394(10) c, Å42.6937(95) 42.2839(52) α, deg 90 90 β, deg 99.612(3) 99.334(2) γ, deg90 90 V, Å³ 8396(3) 8276.5(17) ρ_(calc), g/cm³ 1.31 1.31 crystaldimensions, mm 0.37 × 0.27 × 0.17 0.18 × 0.18 × 0.12 T, K 100(2) 100(2)2Θ max for refinement, deg 56 56 total reflections 35664 25359independent reflections 9903 7271 no. of observed data 6743 4887 no. ofparameters 520 509 R_(int) 0.0655 0.0889 μ, mm⁻¹ 0.252 0.236 R₁(F),wR₂(F²), (I > 2σ(I)) 0.0503, 0.1006 0.0511, 0.1019 Goodness-of-fit on F²1.018 0.995

TABLE S11 Crystallographic Data x(Guest)@H,H,SiMe₂ Crystal ParametersH,H,SiMe₂ 0.91(MeCl)@H,H,SiMe₂ Chemical formula C₃₆H₄₀O₈Si₄C_(36.91)H_(42.73)O₈Si₄Cl_(0.91) Formula weight, g/mol 713.05 759Solvent none EtOAc Crystal system Monoclinic Monoclinic Space groupP2₁/n P2₁/m Z 4 4 a, Å 15.2400(19) 10.8232(11) b, Å 11.1290(14)23.1753(24) c, Å 22.6153(28) 15.2837(16) α, deg 90 90 β, deg 107.000(2)90.427(2) γ, deg 90 90 V, Å³ 3668.1(8) 3833.5(7) ρ_(calc), g/cm³ 1.291.31 crystal dimensions, mm 0.52 × 0.50 × 0.25 0.51 × 0.22 × 0.22 T, K100(2) 100(2) 2Θ max for refinement, 56 56 deg total reflections 3147933693 independent reflections 8646 9268 no. of observed data 5825 5563no. of parameters 441 481 R_(int) 0.0586 0.0783 μ, mm⁻¹ 0.211 0.268R₁(F), wR₂(F²), 0.0503, 0.1204 0.0526, 0.1211 (I > 2σ(I))Goodness-of-fit on F² 1.083 0.965

TABLE S12 Raw data of MeCl vs. EtCl competition experiments. Equivalentswere determined by ¹H NMR unless otherwise specified and K calculated byequation 1. Trial 1-10 were done by the cooling method, trials 11-14done by the evaporation method, trials 15 and 16 done by theprecipitation method, and trial 17 was performed by crystal preparationof a solid-solution, studied further by NMR and SCXRD. Ratio Eq. Eq.Trial before (X) Ratio after (Y) K_(MeCl:EtCl) MeCl/cup EtCl/cup 11:1.13 1:0.06 19 0.54 0.03 2 1:1.34 1:0.05 27 0.67 0.03 3 1:2.81 1:0.0931 0.44 0.04 4 1:141 1:7.53 19 0.1 0.78 5 1:259 1:11.9 22 0.07 0.82 61:237 1:10 24 0.08 0.81 7 1:41 1:2.47 17 0.26 0.63 8 1:46 1:1.92 24 0.270.52 9 1:6.18 5.5:1 34 0.44 0.08 10 1:6.79 4.4:1 30 0.49 0.11 11 1:11171:37 30 0.02 0.9 12 1:242 1:16 15 0.06 0.94 13 1:1900 1:83 23 0.01 0.9914 1:497 1:34 15 0.03 0.95 15 1:24 1:1.17 21 16 1:30 1:1.49 20 17 1:781:4.38 (NMR) 18 1:3.23 (SCXRD) 24 K_(MeCl:EtCl)  23(6) (average):

TABLE S13 Raw data of MeCl vs. DME competition experiments. Equivalentswere determined by ¹H NMR unless otherwise specified and K calculated byequation 1. Trial 1-11 were done by the cooling method, trials 12-15done by the evaporation method, trials 16 and 17 done by theprecipitation method, and trial 18 was performed by crystal preparationof a solid-solution, studied further by NMR and SCXRD. Ratio Eq. Eq.Trial before (X) Ratio after (I) K_(MeCl:DME) MeCl/cup DME/cup 1 1:1.051:0.045 23 0.4 0.02 2 1:1.14 1:0.06 19 0.06 0.004 3 1:0.99 1:0.02 500.33 0.005 4 1:1.01 1:0.015 67 0.14 0.01 5 1:88 1:2.1 42 0.24 0.51 61:52 1:0.98 53 0.36 0.36 7 1:68 1:1.02 67 0.09 0.1 8 1:49 1:1.19 41 0.270.29 9 1:46 1:0.67 69 0.09 0.06 10 1:3.76 11.8:1 44 0.07 0.006 11 1:4.0910.42:1 43 0.33 0.03 12 1:56 1:1.64 34 0.3 0.49 13 1:177 1:7.1 25 0.070.53 14 1:129 1:3.2 40 0.12 0.38 15 1:451 1:8.7 52 0.06 0.52 16 1:211.63:1 34 17 1:14 1.68:1 24 18 1:29 3.19:1 (NMR) 93 2.52:1 (SCXRD) 73K_(MeCl:DME)  45(18) (average):

The invention claimed is:
 1. A composition comprising a compound offormula (I):

and/or stereoisomers thereof; wherein R is H, C₁-C₆ alkyl, halo, or NO₂;R¹ is H, C₁-C₆ alkyl, Ph, (C₁-C₆ alkyl)_(x)Ph, (C(halo)₃)_(x)Ph, or(halo)_(x)Ph; Y is —CH₂—; and x is an integer from 1-3; wherein thecomposition is in a crystalline form that comprises void spaces of atleast 15 Å³; and wherein the void spaces are free of other atoms andmolecules.
 2. The composition of claim 1; wherein for the compound offormula (I): R is H, CH₃, Br, or NO₂; and R¹ is H, CH₃, CH₂CH₃, i-Bu,Ph, 4-CH₃Ph, 4-CF₃Ph, 3,5-(CF₃)₂Ph, or 3,5-F₂Ph.
 3. The composition ofclaim 1; wherein for the compound of formula (I): R is H; and R¹ is H,i-Bu, 4-CF₃Ph, 3,5-(CF₃)₂Ph, or 3,5-F₂Ph.
 4. The composition of claim 1;wherein for the compound of formula (I): R is CH₃; R¹ is CH₂CH₃, i-Bu,3,5-(CF₃)₂Ph.
 5. The composition of claim 1; wherein for the compound offormula (I): R is NO₂; and R¹ is H or CH₃.
 6. The composition of claim1; wherein for the compound of formula (I): R is H, CH₃, or Br; and R¹is H, CH₃, CH₂CH₃, Ph, or 4-CH₃Ph.
 7. The composition of claim 1;wherein the compound of formula (I) is the rccc or the rcttstereoisomer; and wherein the compound of formula (I) is at least 95%stereoisomerically pure.
 8. The composition of claim 1; wherein thecompound of formula (I) is formula (Ia):

and/or stereoisomers thereof.
 9. The composition of claim 1; wherein thecompound of formula (I) is selected from the following (R, R¹, Y): (H,CH₃, CH₂); (H, i-Bu, CH₂); (H, 4-CF₃Ph, CH₂); (H, 3,5-F₂Ph, CH₂); (CH₃,3,5-(CF₃)₂Ph, CH₂); (CH₃, CH₃CH₂, CH₂); (CH₃, i-Bu, CH₂); and (NO₂, H,CH₂).
 10. The composition of claim 1; wherein the compositions comprisevoid spaces of 20 Å³ to 300 Å³.
 11. The composition of claim 1; whereinthermogravimetric analysis (TGA) of the composition reveals no more than1% mass loss up to the temperature of sublimation of the composition.12. The composition of claim 1; wherein the composition is capable offorming a host-guest complex with one or more guest gas molecules withinits void spaces; and wherein the guest gas is selected from one or moreC₁ hydrocarbon gasses, C₂ hydrocarbon gasses, and C₃ hydrocarbon gasses.13. A chemical compound of formula (IIa);

and/or stereoisomers thereof; wherein R⁴ is i-Bu, 4-CF₃Ph, 3,5-(CF₃)₂Ph,or 3,5-F₂Ph; and Z is —CH₂—.
 14. A chemical compound of formula (IIb):

and/or stereoisomers thereof; wherein R⁴ is CH₂CH₃, i-Bu, or3,5-(CF₃)₂Ph; and Z is —CH₂—.
 15. A chemical compound of formula (IIc):

and/or stereoisomers thereof; wherein R⁴ is H, C₁-C₆ alkyl, Ph, (C₁-C₆alkyl)_(x)Ph, (C(halo)₃)_(x)Ph, or (halo)_(x)Ph; and Z is —CH₂—; whereinx is an integer from 1-3.
 16. The compound of claim 15; wherein R⁴ is Hor CH₃ and Z is CH₂.